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1.
J Biosci ; 44(2)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31180046

RESUMO

Keratins, the epithelial-predominant members of the intermediate filament superfamily, are expressed in a pairwise, tissuespecific and differentiation-dependent manner. There are 28 type I and 26 type II keratins, which share a common structure comprising a central coiled coil α-helical rod domain flanked by two nonhelical head and tail domains. These domains harbor sites for major posttranslational modifications like phosphorylation and glycosylation, which govern keratin function and dynamics. Apart from providing structural support, keratins regulate various signaling machinery involved in cell growth, motility, apoptosis etc. However, tissue-specific functions of keratins in relation to cell proliferation and differentiation are still emerging. Altered keratin expression pattern during and after malignant transformation is reported to modulate different signaling pathways involved in tumor progression in a context-dependent fashion. The current review focuses on the literature related to the role of keratins in the regulation of cell proliferation, differentiation and transformation in different types of epithelia.


Assuntos
Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Células Epiteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Queratinas/genética , Neoplasias/genética , Processamento de Proteína Pós-Traducional , Acetilação , Animais , Apoptose/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Células Epiteliais/patologia , Glicosilação , Humanos , Queratinas/química , Queratinas/classificação , Queratinas/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação , Estrutura Secundária de Proteína , Transdução de Sinais
2.
Hum Genomics ; 12(1): 27, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29784039

RESUMO

BACKGROUND: Mutations in keratin proteins have been vastly associated with a wide array of genodermatoses; however, mutations of keratins in psoriasis have not been fully investigated. The main aim of the current research was to identify the mutation in K14, K10, K16, and K17 genes in two stages of psoriasis patients. METHODS: Ninety-six psoriatic skin biopsies were collected. mRNA transcript of K14, K10, K16, and K17 was prepared, amplified, and sequenced. Sanger sequences of all keratins were further validated for mutational analysis using Mutation Surveyor and Alamut Visual. Then, in silico analysis of protein stability and protein and gene expression of all keratins was performed and validated. RESULTS: Out of 44 mutations, about 75% of keratins are highly pathogenic and deleterious. Remaining 25% mutations are less pathogenic and tolerated in nature. In these 33 deleterious mutations were immensely found to decrease keratin protein stability. We also found a correlation between keratin and Psoriasis Area and Severity Index score which added that alteration in keratin gene in skin causes severity of psoriasis. CONCLUSIONS: We strongly concluded that acanthosis and abnormal terminal differentiation was mainly due to the mutation in epidermal keratins. In turn, disease severity and relapsing of psoriasis are mainly due to the mutation of hyperproliferative keratins. These novel keratin mutations in psoriatic epidermis might be one of the causative factors for psoriasis.


Assuntos
Queratinas Tipo I/genética , Queratinas/genética , Mutação/genética , Psoríase/genética , Acantose Nigricans/genética , Acantose Nigricans/fisiopatologia , Adolescente , Adulto , Idoso , Biópsia , Diferenciação Celular , Proliferação de Células/genética , Análise Mutacional de DNA , Epiderme/metabolismo , Epiderme/fisiopatologia , Feminino , Humanos , Queratinas/classificação , Masculino , Pessoa de Meia-Idade , Estabilidade Proteica , Psoríase/patologia , Índice de Gravidade de Doença , Pele/metabolismo , Pele/patologia , Adulto Jovem
3.
PLoS One ; 12(8): e0183053, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28854252

RESUMO

Baleen has been harvested by indigenous people for thousands of years, as well as collected by whalers as an additional product of commercial whaling in modern times. Baleen refers to the food-filtering system of Mysticeti whales; a full baleen rack consists of dozens of plates of a tough and flexible keratinous material that terminate in bristles. Due to its properties, baleen was a valuable raw material used in a wide range of artefacts, from implements to clothing. Baleen is not widely used today, however, analyses of this biomolecular tissue have the potential to contribute to conservation efforts, studies of genetic diversity and a better understanding of the exploitation and use of Mysticeti whales in past and recent times. Fortunately, baleen is present in abundance in museum natural history collections. However, it is often difficult or impossible to make a species identification of manufactured or old baleen. Here, we propose a new tool for biomolecular identification of baleen based on its main structural component alpha-keratin (the same protein that makes up hair and fingernails). With the exception of minke whales, alpha-keratin sequences are not yet known for baleen whales. We therefore used peptide mass fingerprinting to determine peptidic profiles in well documented baleen and evaluated the possibility of using this technique to differentiate species in baleen samples that are not adequately identified or are unidentified. We examined baleen from ten different species of whales and determined molecular markers for each species, including species-specific markers. In the case of the Bryde's whales, differences between specimens suggest distinct species or sub-species, consistent with the complex phylogeny of the species. Finally, the methodology was applied to 29 fragments of baleen excavated from archaeological sites in Labrador, Canada (representing 1500 years of whale use by prehistoric people), demonstrating a dominance of bowhead whale (Balaena mysticetus) in the archaeological assemblage and the successful application of the peptide mass fingerprinting technique to identify the species of whale in unidentified and partially degraded samples.


Assuntos
Estruturas Animais/química , Baleia Franca/classificação , Queratinas/isolamento & purificação , Mapeamento de Peptídeos/métodos , Filogenia , Estruturas Animais/anatomia & histologia , Animais , Arqueologia/instrumentação , Arqueologia/métodos , Biomarcadores , Baleia Franca/anatomia & histologia , Canadá , Queratinas/classificação , Espectrometria de Massas , Museus , Nova Zelândia
4.
Mol Phylogenet Evol ; 115: 40-49, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28739369

RESUMO

Regressive evolution of anatomical traits often corresponds with the regression of genomic loci underlying such characters. As such, studying patterns of gene loss can be instrumental in addressing questions of gene function, resolving conflicting results from anatomical studies, and understanding the evolutionary history of clades. The evolutionary origins of snakes involved the regression of a number of anatomical traits, including limbs, taste buds and the visual system, and by analyzing serpent genomes, I was able to test three hypotheses associated with the regression of these features. The first concerns two keratins that are putatively specific to claws. Both genes that encode these keratins are pseudogenized/deleted in snake genomes, providing additional evidence of claw-specificity. The second hypothesis is that snakes lack taste buds, an issue complicated by conflicting results in the literature. I found evidence that different snakes have lost one or more taste receptors, but all snakes examined retained at least one gustatory channel. The final hypothesis addressed is that the earliest snakes were adapted to a dim light niche. I found evidence of deleted and pseudogenized genes with light-associated functions in snakes, demonstrating a pattern of gene loss similar to other dim light-adapted clades. Molecular dating estimates suggest that dim light adaptation preceded the loss of limbs, providing some bearing on interpretations of the ecological origins of snakes.


Assuntos
Genoma , Queratinas/genética , Opsinas/genética , Receptores Acoplados a Proteínas-G/genética , Serpentes/classificação , Animais , Evolução Biológica , Evolução Molecular , Casco e Garras/metabolismo , Queratinas/classificação , Queratinas/metabolismo , Opsinas/classificação , Filogenia , Receptores Acoplados a Proteínas-G/classificação , Serpentes/genética
5.
Clin. transl. oncol. (Print) ; 19(3): 326-331, mar. 2017. tab, graf
Artigo em Inglês | IBECS | ID: ibc-160188

RESUMO

Purpose. Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC. Methods. The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed. Result. We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01). Conclusion. Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Paclitaxel/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Prognóstico , Queratinas/administração & dosagem , Queratinas/análise , Queratinas/classificação , Testes Sorológicos/métodos , Queratinócitos/citologia , Biomarcadores Tumorais/análise , Biomarcadores/análise , Biomarcadores/sangue
6.
Neoplasia ; 18(7): 399-412, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27435923

RESUMO

Pleural effusion (PE), excess fluid in the pleural space, is often observed in lung cancer patients and also forms due to many benign ailments. Classifying it quickly is critical, but this remains an analytical challenge often lengthening the diagnosis process or exposing patients to unnecessary risky invasive procedures. We tested the analysis of PE using a multiplexed cytokeratin (CK) panel with targeted mass spectrometry-based quantitation for its rapid classification. CK markers are often assessed in pathological examinations for cancer diagnosis and guiding treatment course. We developed methods to simultaneously quantify 33 CKs in PE using peptide standards for increased analytical specificity and a simple CK enrichment method to detect their low amounts. Analyzing 121 PEs associated with a variety of lung cancers and noncancerous causes, we show that abundance levels of 10 CKs can be related to PE etiology. CK-6, CK-7, CK-8, CK-18, and CK-19 were found at significantly higher levels in cancer-related PEs. Additionally, elevated levels of vimentin and actin differentiated PEs associated with bacterial infections. A classifier algorithm effectively grouped PEs into cancer-related or benign PEs with 81% sensitivity and 79% specificity. A set of undiagnosed PEs showed that our method has potential to shorten PE diagnosis time. For the first time, we show that a cancer-relevant panel of simple-epithelial CK markers currently used in clinical assessment can also be quantitated in PEs. Additionally, while requiring less invasive sampling, our methodology demonstrated a significant ability to identify cancer-related PEs in clinical samples and thus could improve patient care in the future.


Assuntos
Actinas/metabolismo , Biomarcadores Tumorais/análise , Queratinas/análise , Neoplasias Pulmonares/patologia , Derrame Pleural/diagnóstico , Vimentina/metabolismo , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Queratinas/classificação , Queratinas/metabolismo , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Derrame Pleural/classificação , Derrame Pleural/patologia
7.
Appl Immunohistochem Mol Morphol ; 24(9): 622-626, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26371435

RESUMO

Metaplastic breast carcinoma (MBC) is a heterogenous group of tumors that diverge from conventional glandular differentiation. The metaplastic component can be focal or may be present purely posing diagnostic challenges. Since MBC may show focal immunostaining or may even be negative for some cytokeratins (CK), different CKs are often needed to prove their epithelial origin. OSCAR is a relatively new broad-spectrum anti-CK antibody. Thirty MBC cases diagnosed at our institution were retrieved, including 7 spindle cell carcinomas. Representative slides were immunostained for CK-OSCAR, CK-AE1/AE3, CAM5.2, CK-903, and CK5/6. Nineteen spindle cell lesions were used as controls, including 6 malignant and 10 borderline phyllodes tumor, 1 inflammatory pseudotumor, 1 solitary fibrous tumor, and 1 nodular fasciitis case. All 30 cases (100%) of metaplastic carcinomas were positive for CK-OSCAR, compared with 27/30 (90%, P=0.076) for CK-AE1/AE3, 21/30 (70%, P≤0.01) for CK-903, 19/30 (63.3%, P≤0.01) for CAM5.2, and 15/30 (50%, P≤0.01) for CK5/6. All control cases were negative for CK-OSCAR. All 7 spindle cell carcinomas were also positive for CK-OSCAR (100%) compared with 6/7 (85.7%) for CK-AE1/AE3, 4/7 (57%) for CK-903, 3/7 (42.8%) for CAM5.2, and 2/7 (28.5%) for CK5/6. Our data show that CK-OSCAR is more sensitive than other individual CKs in diagnosing MBC. Coupled with high specificity, CK-OSCAR may potentially be used in lieu of a panel of CKs to identify the epithelial origin of these tumors, especially in spindle cell tumors. This is particularly useful in limited core biopsy specimens, to help guide treatment and simultaneously lower testing costs.


Assuntos
Anticorpos/imunologia , Neoplasias da Mama/diagnóstico , Queratinas/imunologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratinas/classificação
8.
Am J Physiol Gastrointest Liver Physiol ; 306(8): G641-9, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24578343

RESUMO

Barrett's esophagus is characterized by a distinct Th2-predominant cytokine profile (IL-4) from in vivo or ex vivo evidence. The detailed role of cytokines in Barrett's esophagus, particularly whether Th2 cytokines are causative factors driving metaplastic processes, remains unknown. In this study, air-liquid interface-cultured human esophageal epithelial cells were stimulated by a Th2 cytokine, IL-4, and Th1 cytokines, TNF-α and IL-1ß, continuously for 10 days. Barrier function was determined by transepithelial electrical resistance. Morphological changes were investigated by hematoxylin and eosin staining. Keratin profile (keratin 7, 8, 13, and 14) and squamous differentiation markers (involucrin) were investigated by RT-quantitative PCR, Western blotting, and immunohistochemical staining. Pharmacological inhibitors were used to identify the underlying cellular signaling. We report that IL-4, TNF-α, and IL-1ß decrease barrier function, but only IL-4 significantly increases cell layers and changes cell morphology. IL-4 time dependently downregulates the expression levels of the squamous cell markers involucrin and keratin 13 and upregulates the expression levels of the columnar cell markers keratin 7 and 8. Neither TNF-α nor IL-1ß shows any effect on these indexes. JAK inhibitor I and PI3K inhibitors significantly block the IL-4-induced changes in the levels of keratin 8 and 13. In conclusion, IL-4 inhibits squamous differentiation program of esophageal epithelial cells and induces differentiation toward columnar cells through the JAK/PI3K pathway. Thus IL-4 may be involved in the early stages of Barrett's esophagus development.


Assuntos
Esôfago de Barrett , Células Epiteliais , Esôfago/patologia , Interleucina-4/metabolismo , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biomarcadores/metabolismo , Diferenciação Celular , Células Cultivadas , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Imuno-Histoquímica , Interleucina-1beta/metabolismo , Queratinas/classificação , Queratinas/metabolismo , Metaplasia/metabolismo , Metaplasia/patologia , Precursores de Proteínas/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
9.
Int J Oral Sci ; 5(1): 1-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23538640

RESUMO

This study aimed to compare epithelial cells derived from human embryonic stem cells (hESCs) to human ameloblast-lineage cells (ALCs), as a way to determine their potential use as a cell source for ameloblast regeneration. Induced by various concentrations of bone morphogenetic protein 4 (BMP4), retinoic acid (RA) and lithium chloride (LiCl) for 7 days, hESCs adopted cobble-stone epithelial phenotype (hESC-derived epithelial cells (ES-ECs)) and expressed cytokeratin 14. Compared with ALCs and oral epithelial cells (OE), ES-ECs expressed amelogenesis-associated genes similar to ALCs. ES-ECs were compared with human fetal skin epithelium, human fetal oral buccal mucosal epithelial cells and human ALCs for their expression pattern of cytokeratins as well. ALCs had relatively high expression levels of cytokeratin 76, which was also found to be upregulated in ES-ECs. Based on the present study, with the similarity of gene expression with ALCs, ES-ECs are a promising potential cell source for regeneration, which are not available in erupted human teeth for regeneration of enamel.


Assuntos
Ameloblastos/fisiologia , Células-Tronco Embrionárias/fisiologia , Amelogênese/genética , Amelogenina/análise , Proteína Morfogenética Óssea 4/farmacologia , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Linhagem da Célula , Células-Tronco Embrionárias/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Fator 8 de Crescimento de Fibroblasto/análise , Proteínas Hedgehog/análise , Proteínas de Homeodomínio/análise , Humanos , Queratinas/análise , Queratinas/classificação , Cloreto de Lítio/farmacologia , Fator de Transcrição MSX1/análise , Mucosa Bucal/citologia , Fenótipo , Regeneração/fisiologia , Pele/citologia , Fatores de Transcrição/análise , Tretinoína/farmacologia
10.
Appl Spectrosc ; 66(5): 606-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22524968

RESUMO

The ability to discriminate between objects manufactured from animal horn and chelonian (turtle, tortoise, or terrapin) shell is important from a cultural and archeological perspective such that it may allow conservators to determine the appropriate treatment and long-term care solution. It would also aid curators in identifying and cataloging items manufactured from these materials. Discrimination and classification is also a valuable tool for those involved in tracking the illegal trade in restricted materials of this nature. Attenuated total reflection infrared (ATR-IR) spectroscopy, using a single reflection diamond internal reflection element (IRE), coupled with discrimination analysis was used to analyze a total of thirty-nine samples (29 calibration samples, 10 validation samples). A discrimination analysis model was constructed using Mahalanobis distances to classify spectra into one of two classes. The model was then subsequently used to successfully classify all validation samples and correctly identify them as animal horn or chelonian shell based on second-derivative spectra of the amide I and II regions. This technique requires minimal to no sample preparation and may be used to nondestructively identify very small samples successfully without performing detailed secondary structural curve-fitting routines. This model should be a valuable resource to museums, conservators, and wildlife management programs for rapidly and reliably discriminating between animal horn and chelonian shell.


Assuntos
Exoesqueleto/química , Cornos/química , Queratinas/classificação , Espectrofotometria Infravermelho/métodos , Animais , Búfalos , Análise Discriminante , Cabras , Queratinas/análise , Queratinas/química , Tartarugas
11.
Int J Biol Sci ; 8(2): 258-64, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22298953

RESUMO

Most protein in hair and wool is of two broad types: keratin intermediate filament-forming proteins (commonly known as keratins) and keratin-associated proteins (KAPs). Keratin nomenclature was reviewed in 2006, but the KAP nomenclature has not been revised since 1993. Recently there has been an increase in the number of KAP genes (KRTAPs) identified in humans and other species, and increasingly reports of variation in these genes. We therefore propose that an updated naming system is needed to accommodate the complexity of the KAPs. It is proposed that the system is founded in the previous nomenclature, but with the abbreviation sp-KAPm-nL*x for KAP proteins and sp-KRTAPm-n(p/L)*x for KAP genes. In this system "sp" is a unique letter-based code for different species as described by the protein knowledge-based UniProt. "m" is a number identifying the gene or protein family, "n" is a constituent member of that family, "p" signifies a pseudogene if present, "L" if present signifies "like" and refers to a temporary "place-holder" until the family is confirmed and "x" signifies a genetic variant or allele. We support the use of non-italicised text for the proteins and italicised text for the genes. This nomenclature is not that different to the existing system, but it includes species information and also describes genetic variation if identified, and hence is more informative. For example, GenBank sequence JN091630 would historically have been named KRTAP7-1 for the gene and KAP7-1 for the protein, but with the proposed nomenclature would be SHEEP-KRTAP7-1*A and SHEEP-KAP7-1*A for the gene and protein respectively. This nomenclature will facilitate more efficient storage and retrieval of data and define a common language for the KAP proteins and genes from all mammalian species.


Assuntos
Queratinas/classificação , Terminologia como Assunto , Animais , Regulação da Expressão Gênica/fisiologia , Especificidade da Espécie
12.
Artigo em Inglês | MEDLINE | ID: mdl-21684774

RESUMO

OBJECTIVE: The aim of this study was to describe the clinicopathologic and immunohistochemical characteristics of 14 cases of central odontogenic fibroma (COF), and the ultrastructural features of 2 of them. STUDY DESIGN: Collaborative retrospective study based on the records of 4 oral pathology diagnostic services in Latin America based on the current World Health Organization classification. RESULTS: There were 7 male and 7 female patients (mean age 31.8 years). Eight tumors occurred in the maxilla and 6 in the mandible. Thirteen cases were epithelium-rich and 1 epithelium-poor COF. Three were classified as hybrid COF with giant cell lesion. Mean size of the hybrid lesions were larger than pure COF (3.8 vs. 2.4 cm). Odontogenic epithelial islands were immunoreactive for cytokeratin (CK) AE1/AE3, CK5, CK14, CK19, and 34BE12 and negative for CK1 and CK18. Langerhans cells positive for S-100 and CD1a were found within the epithelial islands in 6/6 tested cases. CD68 was expressed in the giant cells of the hybrid lesions and in a few mononuclear cells of 2 cases of COF. Ki-67 index was <1% in all cases. In 6 tumors (42.8%), there were small globular eosinophilic droplets within the epithelial islands, which were positive for collagen type IV, and 9/13 cases (69.2%) were focally positive for smooth muscle actin. In addition to fibroblasts, myofibroblastic differentiation was found in the 2 cases studied ultrastructurally. CONCLUSIONS: Immunohistochemistry was useful to confirm the presence of epithelium and to exclude other central fibrous tumors. COF also contains a variable number of mast cells, Langerhans cells, and myofibroblasts, and further studies are needed to better understand the participation of these cells in COF histogenesis.


Assuntos
Fibroma/patologia , Queratinas/metabolismo , Neoplasias Mandibulares/patologia , Neoplasias Maxilares/patologia , Tumores Odontogênicos/patologia , Adolescente , Adulto , Epitélio/patologia , Feminino , Fibroma/diagnóstico por imagem , Fibroma/metabolismo , Humanos , Imuno-Histoquímica , Queratinas/classificação , Masculino , Neoplasias Mandibulares/diagnóstico por imagem , Neoplasias Mandibulares/metabolismo , Neoplasias Maxilares/diagnóstico por imagem , Neoplasias Maxilares/metabolismo , Pessoa de Meia-Idade , Tumores Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/metabolismo , Estudos Retrospectivos , Ultrassonografia , Adulto Jovem
13.
Exp Dermatol ; 20(7): 582-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21554405

RESUMO

Keratin IF (KRT) and keratin-associated protein genes encode the majority of wool and hair proteins. We have identified cDNA sequences representing nine novel sheep KRT genes, increasing the known active genes from eight to 17, a number comparable to that in the human. However, the absence of KRT37 in the type I family and the discovery of type II KRT87 in sheep exemplify species-specific compositional differences in hair KRT genes. Phylogenetic analysis of hair KRT genes within type I and type II families in the sheep, cattle and human genomes revealed a high degree of consistency in their sequence conservation and grouping. However, there were differences in the fibre compartmentalisation and keratinisation zones for the expression of six ovine KRT genes compared with their human orthologs. Transcripts of three genes (KRT40, KRT82 and KRT84) were only present in the fibre cuticle. KRT32, KRT35 and KRT85 were expressed in both the cuticle and the fibre cortex. The remaining 11 genes (KRT31, KRT33A, KRT33B, KRT34, KRT36, KRT38-39, KRT81, KRT83 and KRT86-87) were expressed only in the cortex. Species-specific differences in the expressed keratin gene sets, their relative expression levels and compartmentalisation are discussed in the context of their underlying roles in wool and hair developmental programmes and the distinctive characteristics of the fibres produced.


Assuntos
Expressão Gênica/genética , Queratinas/classificação , Queratinas/genética , Ovinos/genética , Ovinos/metabolismo , Animais , Sequência de Bases/genética , Bovinos , DNA Complementar/genética , Folículo Piloso/metabolismo , Humanos , Queratinócitos/metabolismo , Queratinas Específicas do Cabelo/classificação , Queratinas Específicas do Cabelo/genética , Queratinas Tipo I/classificação , Queratinas Tipo I/genética , Queratinas Tipo II/classificação , Queratinas Tipo II/genética , Anotação de Sequência Molecular , Dados de Sequência Molecular , Filogenia , Homologia de Sequência do Ácido Nucleico , Pele/metabolismo , Lã/química , Lã/crescimento & desenvolvimento
14.
Exp Dermatol ; 20(3): 217-28, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21323743

RESUMO

Keratins are a highly diverse family of cytoskeletal proteins and important markers of epithelial cell differentiation. In this review, applying the new keratin nomenclature recently introduced, we summarize and discuss the distribution and significance of keratin patterns in cutaneous epithelial tumors in relation to the epithelial structures of normal human skin. The available literature data show that the analysis of keratin profiles broadens our understanding of the differentiation, nature and histogenetic origin of the various, highly singular epithelial tumors arising in the skin. Moreover, keratins may aid in histological diagnosis and, in certain instances, may be helpful for the recognition of tumor malignancy and aggressiveness. Furthermore, we briefly address the topic of keratin-related skin disorders.


Assuntos
Queratinas/metabolismo , Neoplasias Epiteliais e Glandulares/metabolismo , Neoplasias Cutâneas/metabolismo , Animais , Humanos , Queratinas/classificação , Queratinas/genética , Neoplasias Epiteliais e Glandulares/diagnóstico , Pele/citologia , Pele/metabolismo , Neoplasias Cutâneas/diagnóstico
15.
J Cell Sci ; 124(Pt 24): 4221-32, 2011 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22215855

RESUMO

Keratins (Ks) consist of central α-helical rod domains that are flanked by non-α-helical head and tail domains. The cellular abundance of keratins, coupled with their selective cell expression patterns, suggests that they diversified to fulfill tissue-specific functions although the primary structure differences between them have not been comprehensively compared. We analyzed keratin sequences from many species: K1, K2, K5, K9, K10, K14 were studied as representatives of epidermal keratins, and compared with K7, K8, K18, K19, K20 and K31, K35, K81, K85, K86, which represent simple-type (single-layered or glandular) epithelial and hair keratins, respectively. We show that keratin domains have striking differences in their amino acids. There are many cysteines in hair keratins but only a small number in epidermal keratins and rare or none in simple-type keratins. The heads and/or tails of epidermal keratins are glycine and phenylalanine rich but alanine poor, whereas parallel domains of hair keratins are abundant in prolines, and those of simple-type epithelial keratins are enriched in acidic and/or basic residues. The observed differences between simple-type, epidermal and hair keratins are highly conserved throughout evolution. Cysteines and histidines, which are infrequent keratin amino acids, are involved in de novo mutations that are markedly overrepresented in keratins. Hence, keratins have evolutionarily conserved and domain-selectively enriched amino acids including glycine and phenylalanine (epidermal), cysteine and proline (hair), and basic and acidic (simple-type epithelial), which reflect unique functions related to structural flexibility, rigidity and solubility, respectively. Our findings also support the importance of human keratin 'mutation hotspot' residues and their wild-type counterparts.


Assuntos
Aminoácidos/análise , Queratinas Específicas do Cabelo/química , Queratinas/química , Animais , Bovinos , Epiderme/química , Evolução Molecular , Humanos , Queratinas/classificação , Camundongos , Estrutura Terciária de Proteína , Análise de Sequência de Proteína
16.
Nucleic Acids Res ; 38(20): 7008-21, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20621981

RESUMO

Cancer is among the major causes of human death and its mechanism(s) are not fully understood. We applied a novel meta-analysis approach to multiple sets of merged serial analysis of gene expression and microarray cancer data in order to analyze transcriptome alterations in human cancer. Our methodology, which we denote 'COgnate Gene Expression patterNing in tumours' (COGENT), unmasked numerous genes that were differentially expressed in multiple cancers. COGENT detected well-known tumor-associated (TA) genes such as TP53, EGFR and VEGF, as well as many multi-cancer, but not-yet-tumor-associated genes. In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues. Furthermore, a significant number of RIDGEs are associated with GC-rich regions on the genome. All assembled data is freely available online (www.oncoreveal.org) as a tool implementing COGENT analysis of multi-cancer genes and RIDGEs. These findings engender a deeper understanding of cancer biology by demonstrating the existence of a pool of under-studied multi-cancer genes and by highlighting the cancer-specificity of some TA-RIDGEs.


Assuntos
Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Genoma Humano , Humanos , Internet , Queratinas/classificação , Queratinas/genética , Análise de Sequência com Séries de Oligonucleotídeos , Sitios de Sequências Rotuladas , Software
17.
Auris Nasus Larynx ; 37(4): 519-21, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20172670

RESUMO

First described in 1969, syringoid eccrine carcinoma (SEC) is a rare cutaneous tumor with some controversy regarding its correct definition. It consists of solid nests and small cords in a dense fibrocollagenous stroma. As it is rare, its clinical appearance is not well characterized and its biological behaviour is not defined. It usually affects skin of the scalp, extremities and more rarely, other sites. It behaves as locally aggressive tumor but metastases are rare. Although there have been some previous reports describing clinical presentation and management of SEC in the skin, there has been no previous reports describing clinical findings and management of this tumor in the external auditory canal. We report a case of a 57-year-old female with small solitary mass in left external auditory canal associated with discharge, severe itching and bleeding on manipulation. Complete local excision is the recommended method for diagnosis and treatment of this tumor in the external auditory canal. This extremely rare case serves as a springboard for the diagnosis as well as the management of SEC in external auditory canal.


Assuntos
Carcinoma/patologia , Meato Acústico Externo/patologia , Neoplasias da Orelha/patologia , Glândulas Écrinas/patologia , Queratinas/biossíntese , Neoplasias das Glândulas Sudoríparas/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Carcinoma/cirurgia , Meato Acústico Externo/metabolismo , Meato Acústico Externo/cirurgia , Neoplasias da Orelha/metabolismo , Neoplasias da Orelha/cirurgia , Glândulas Écrinas/metabolismo , Glândulas Écrinas/cirurgia , Feminino , Humanos , Técnicas Imunoenzimáticas , Queratinas/classificação , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Couro Cabeludo/patologia , Couro Cabeludo/cirurgia , Neoplasias das Glândulas Sudoríparas/metabolismo , Neoplasias das Glândulas Sudoríparas/cirurgia
18.
Int J Oral Maxillofac Surg ; 38(4): 388-92, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19217261

RESUMO

Cysts of the tongue are rare, usually derived from epithelia of the embryonic gastrointestinal and respiratory tracts, and classified according to the predominant epithelium lining. These cysts are usually discovered during infancy, more frequently in males, but they may not appear until well into adulthood. The authors report two lingual cysts lined mainly with respiratory, and focally by squamous, epithelium. Periodic acid-Schiff and mucicarmine staining revealed focal positivity in intracystic mucoid material and goblet cells. Immunohistochemical analysis with vimentin, cytokeratins (AE1/AE3, 34betaE12, CK1, CK5, CK6, CK7, CK8, CK10, CK13, CK14, CK16, CK18, and CK19), E-cadherin, beta-catenin, and epithelial membrane antigen showed a similar profile of normal respiratory epithelium, suggesting well-differentiated states. Owing to their controversial origin, these cysts should be named descriptively, as suggested by Manor et al., as lingual cysts with respiratory epithelium.


Assuntos
Coristoma/patologia , Cistos/patologia , Mucosa Respiratória/patologia , Neoplasias da Língua/patologia , Pré-Escolar , Coristoma/metabolismo , Coristoma/cirurgia , Cistos/metabolismo , Cistos/cirurgia , Humanos , Imuno-Histoquímica , Queratinas/classificação , Queratinas/metabolismo , Masculino , Mucosa Respiratória/metabolismo , Neoplasias da Língua/metabolismo , Neoplasias da Língua/cirurgia , Vimentina/metabolismo , Adulto Jovem
19.
Head Neck Pathol ; 2(4): 257-64, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20614291

RESUMO

Mucoepidermoid carcinoma is the most common malignant salivary gland tumor, composed of several different cell types, with controversial histogenesis. The aim of this study was to assess the expression of cytokeratins in mucoepidermoid carcinoma, comparing to cytokeratin expression in normal salivary glands, in order to establish a possible correlation between tumor cells immunostaining and mucoepidermoid carcinoma histogenesis and differentiation. Eighty cases of salivary gland mucoepidermoid carcinoma were immunohistochemically examined with the use of antibodies against cytokeratins 6, 7, 8, 13, 14, 18, and 19. Cytokeratin expression varied according to the cellular type: squamous cells presented high expression of cytokeratins 6, 7, 8, 14, 18, and 19; intermediate and mucous cells of cytokeratin 7; clear and columnar cells of cytokeratins 6, 7, 8 and the latter also expressed cytokeratin 18. Cytokeratin 13 expression was low in all cell types. Cytokeratin immunoexpression in mucoepidermoid carcinoma was variable according to the cellular type; but regardless of the cellular type studied, cytokeratins 7 and 13 were, respectively, constantly high and low expressed. The immunoprofile of the normal salivary glands was variable according to the component but, in general, cytokeratin profile in mucoepidermoid carcinoma showed similarity to the immunoexpression on the excretory duct unit of normal salivary glands.


Assuntos
Carcinoma Mucoepidermoide/patologia , Queratinas/metabolismo , Neoplasias das Glândulas Salivares/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Criança , Feminino , Humanos , Imuno-Histoquímica , Queratinas/classificação , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/metabolismo , Glândulas Salivares Menores/metabolismo , Glândulas Salivares Menores/patologia , Adulto Jovem
20.
J Invest Dermatol ; 126(11): 2366-8, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17041617

RESUMO

When the first nomenclature of the keratin protein family was published over 20 years ago, only 19 keratins were thought to exist. Sequencing of the human genome has now revealed that there are 54 keratin genes. As a consequence, the nomenclature needed revision to apply a logical numbering system that includes the more recently identified keratins of the hair follicle.


Assuntos
Genoma Humano , Queratinas/classificação , Terminologia como Assunto , Genoma Humano/genética , Humanos , Queratinas/genética , Análise de Sequência de DNA
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