RESUMO
Metabolic reprogramming has become the new hallmark of cancer. Carbohydrate metabolism is a key component of metabolic transformations in tumors. To date, many therapeutic agents have been identified that target proteins and enzymes involved in glucose transport and metabolism, with promising results in cell culture studies and animal tumor models. In our studies, we found that the most promising among them is the glycolysis inhibitor iodoacetate. The study of this agent showed that iodoacetate in liposomal form has the best performance. With a course introduction, its antimetastatic and antitumor activity reached significant indices of growth inhibition. At the same time, liposomes with iodoacetate had an almost completely safe toxicological profile compared to the independent form and, as a result, have great potential in polychemotherapy.
Assuntos
Antineoplásicos , Neoplasias , Animais , Lipossomos/farmacologia , Neoplasias/tratamento farmacológico , Iodoacetatos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular TumoralRESUMO
Actin-binding proteins (ABPs) and various signaling systems are involved in the process of squamous cell carcinoma of the larynx and hypopharynx (SCCLH) metastasis. The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA levels of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAI1 and RND3 and SCCLH metastasis. The serum levels of the above ABPs were estimated and the relationship between them and their mRNA expressions was analyzed. The expression levels of ABP mRNAs were measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T1-4N0-1M0). Expression analysis was performed using the 2-ΔΔCT method. The levels of ABPs in the blood serum were measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. No significant difference in the mRNA gene expression in tumor tissue of patients with T1-3N0M0 SCCLH and patients with T2-4N1-2M0 SCCLH was found. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T2-4N1-2M0 patients, the level of PFN1 was lower by 21% and the level of CAP1 was higher by 75% than those observed in T1-4N0M0 patients. The data obtained showed that RND3 is involved in the regulation of molecular cascades of SCCLH metastasis. PFN1 and CAP1 serum levels can be good classifiers of metastases in patients with SCCLH.
Assuntos
Neoplasias Hipofaríngeas/metabolismo , Neoplasias Laríngeas/metabolismo , Proteínas dos Microfilamentos/genética , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/sangue , Proteínas de Ciclo Celular/genética , Cofilina 1/análise , Cofilina 1/sangue , Cofilina 1/genética , Proteínas do Citoesqueleto/análise , Proteínas do Citoesqueleto/sangue , Proteínas do Citoesqueleto/genética , Citoesqueleto/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/sangue , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/sangue , Masculino , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Profilinas/análise , Profilinas/sangue , Profilinas/genética , RNA Mensageiro/genética , Federação Russa , Soro/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição da Família Snail/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Proteínas rho de Ligação ao GTP/genéticaRESUMO
Analysis of HER2 status of the tumor and expression of mTOR, AMPK showed a decrease in mTOR mRNA level in HER2+ tumors in comparison with HER- status. The appearance of PD-L1+ transformed cells in the tumor was associated with increased expression of the LC3B gene and elevated content of the corresponding protein measured after treatment.
Assuntos
Adenocarcinoma , Proteínas Associadas aos Microtúbulos , Neoplasias Gástricas , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antineoplásicos/uso terapêutico , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Resultado do TratamentoRESUMO
The biological aggressiveness of a tumor is determined by the ability of tumor cells to invade and metastasize which is a consequence of their acquisition of a number of phenotypic characteristics. Remodeling of the actin cytoskeleton occurs during cell migration which is carried out by various groups of actin binding proteins in the regulation of which proteasomes and calpains play an important role. Therefore the study of the relationship of proteins associated with cell motility with the processes of lymphogenous metastasis as well as the assessment of the regulatory role of intracellular proteases in these processes is extremely important for fundamental oncology. This study demonstrates the associations of actin-binding proteins with the activity of proteasomes and calpain, which are specific for tumors and metastases of the mammary gland. We proposed a possible scheme of the relationship of intracellular systems with the actin-binding proteins. The results obtained expand the fundamental understanding of the processes of tumor progression and can also be used in the search for proteins-targets for therapeutic action in molecular targeted cancer therapy.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Proteólise , Feminino , Humanos , Metástase LinfáticaRESUMO
The actin-binding proteins profilin, fascin, and ezrin were tested for involvement in metastasis of non-small cell lung cancer (NSCLC). The levels of the PFN1, FSCN1, and EZR mRNAs and respective proteins were determined by real-time PCR and Western blotting; tumor and adjacent normal lung tissue samples were obtained from 46 NSCLC patients. Patients with lymphatic metastasis had higher expression levels of the profilin, fascin, and ezrin mRNAs and the profilin and fascin proteins. Both mRNA and protein expression levels increased in patients with distant metastasis. The molecules may serve as predictors to evaluate the prognosis in NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias Pulmonares/patologia , Proteínas dos Microfilamentos/metabolismo , Profilinas/metabolismo , Linhagem Celular Tumoral , Humanos , Metástase Neoplásica , RNA MensageiroRESUMO
The molecular features of the follicular variant of papillary thyroid cancer are closely related to the clinical behavior of the tumor and the prognosis of the disease. BRAF-V600E mutations in patients with a follicular variant of papillary thyroid cancer have not been identified; however, the majority of patients had T3-4N0M0 stage of the disease. Changes in the expression of transcription and growth factors and AKT/m-TOR signaling pathway components were detected. In addition, hyperexpression of m-TOR and 4EBP1 kinases and CAIX enzyme was shown compared to the classical variant of papillary thyroid cancer, where an increase in the nuclear factor NF-κB p65 and c-RAF kinase expression was observed.
Assuntos
Carcinoma Papilar, Variante Folicular/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Substituição de Aminoácidos , Carcinoma Papilar, Variante Folicular/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ácido Glutâmico/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Proteínas Proto-Oncogênicas B-raf/genética , Transdução de Sinais/genética , Neoplasias da Glândula Tireoide/patologia , Valina/genéticaRESUMO
We analyzed the content of ß-catenin fractions and activity and content of proteasomes in the tissues of patients with non-small cells lung cancer. The content of ß-catenin fractions was elevated and proteasome-dependent proteolysis in the tumor tissue was enhanced in comparison with the corresponding unchanged lung tissue. A negative regression relationship of caspase-like activity of proteasomes and a positive correlation between the content of proteasomes and both fractions of ß-catenin were found. We hypothesize that proteasomes are involved in the degradation of ß-catenin due to caspase-like activity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , beta Catenina/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspases/metabolismo , Quimotripsina/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismoRESUMO
We analyzed the expression of genes encoding proteins involved in cytoskeleton remodeling (RND3, SNAI1, vimentin, cofilin, adenylate cyclase-associated protein 1, ezrin, and profilin) depending on the level of expression of protein phosphatase 1B (PPM1B) mRNA on the example of squamous cell carcinoma of the larynx and hypopharynx. Against the background of a high level of PPM1B expression, a significantly high level of profilin expression was noted. Metastasis correlated with the level of snai1 expression, while relapse after combination treatment was negatively associated with the level of vimentin expression. The obtained new data can reflect molecular peculiarities of the tumor growth in squamous cell carcinoma of the larynx and hypopharynx.
Assuntos
Citoesqueleto/genética , Neoplasias de Cabeça e Pescoço/genética , Recidiva Local de Neoplasia/genética , Profilinas/genética , Proteína Fosfatase 2C/genética , RNA Mensageiro/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cofilina 1/genética , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hipofaringe/metabolismo , Hipofaringe/patologia , Laringe/metabolismo , Laringe/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Profilinas/metabolismo , Proteína Fosfatase 2C/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Vimentina/genética , Vimentina/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
The peculiarities of gastric cancer development associated with the expression levels of components of the AKT/mTOR signaling cascade and PD, PD-L1, PD-L2 have not yet been identified. We revealed the fundamental changes in the expression AKT/mTOR and PD receptors and their ligands associated with dissemination of gastric cancer. An increase in the mRNA level of all components of this cascade was demonstrated. The expression of mTOR and AKT decreased against the background of enhanced expression of PTEN phosphatase. The increase in the expression of PD-1 receptors and PD-L1 and PD-L2 ligands was most pronounced in patients with distant metastases.
Assuntos
Antígeno B7-H1/genética , Proteína 2 Ligante de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antígeno B7-H1/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática , Masculino , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas Proto-Oncogênicas c-raf/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
We analyzed the association of the level of mRNA expression of the main endocytosis receptor LRP1 and actin-binding proteins (ezrin, profilin-1, cofilin-1, and adenylyl cyclase-associated protein 1) with the development and metastasis of laryngeal and laryngopharyngeal squamous cell carcinoma. The mRNA expression was evaluated in paired tissue samples using quantitative reverse transcription real-time PCR (RT-qPCR) and SYBR Green reagents. The study included 38 patients with stage T1-4N0-1M0 laryngeal and laryngopharyngeal squamous cell carcinoma and 10 patients with chronic hyperplastic laryngitis or grade II-III epithelial dysplasia. The expression of LRP1 in patients with laryngeal and laryngopharyngeal squamous cell carcinoma depended on the stage of the tumor process. Against the background of low expression of LRP1 mRNA, the relationship between cofilin 1 and profilin 1 expression became stronger (r=0.08; p=0.05) and a correlation between cofilin 1 and esrin expression (r=0.7; p=0.05) appeared. Studies on a larger patient cohort are required to make a definite conclusion on the role of LRP1 in the development of laryngeal and laryngopharyngeal squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/genética , Cofilina 1/genética , Proteínas do Citoesqueleto/genética , Neoplasias Laríngeas/genética , Laringite/genética , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Neoplasias Faríngeas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Laringite/metabolismo , Laringite/patologia , Laringe/metabolismo , Laringe/patologia , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Faríngeas/metabolismo , Neoplasias Faríngeas/patologia , Faringe/metabolismo , Faringe/patologia , Profilinas/genética , Profilinas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de SinaisRESUMO
Metabolic reprogramming is one of the central features of transformed cells. Elucidation of interactions between oncogenic signaling and cell metabolic processes has become the basis for extensive studies of metabolism reprogramming in tumor tissue. The review summarizes the key results of studies on the catabolic and anabolic rearrangements in tumor cells with special emphasis on carbohydrate, lipid, amino acid, and acetate metabolism determining the cancer phenotype of cells.
Assuntos
Neoplasias/metabolismo , Neoplasias/patologia , Humanos , FenótipoRESUMO
Von Hippel-Lindau protein (VHL) is associated with the development and progression of kidney cancer. An increase in VHL expression was found in patients with the disseminated form of the disease compared to the localized cancer, which was combined with a uniform distribution of decreased (<1.0) and increased (>1.0) VHL mRNA levels in renal cancer patients depending on the dissemination of the process. The increase in VHL expression was accompanied an increase in the level of mRNA for NF-κB p65 and kinases PDK1 and Akt. The revealed data indicate the importance of molecular biological parameters in oncogenesis.
Assuntos
Anidrase Carbônica IX/genética , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Anidrase Carbônica IX/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Perfilação da Expressão Gênica , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Metástase Linfática , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismoRESUMO
We studied the expression of mRNA and the level of CAP1 (adenylate cyclase-associated protein 1) and cofilin proteins in the tissues of patients with non-small cell lung cancer. The expression of mRNA and the level of CAP1 in tumor tissue increased during growth of the primary tumor and its metastasis. It was shown that with the growth of the primary tumor, the content of cofilin in the tumor tissue decreases against the background of increased expression of its mRNA; in regional metastasis, the content of cofilin and expression of the corresponding mRNA increased. It was found that increased content of the studied proteins in the tumor tissue increased the risk of metastasis.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Ciclo Celular/genética , Cofilina 1/genética , Proteínas do Citoesqueleto/genética , Neoplasias Pulmonares/genética , RNA Mensageiro/biossíntese , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica/patologiaRESUMO
This review summarizes information available to date about the structural organization, regulation of functional activity of adenylyl cyclase-associated protein 1 (CAP1), and its participation in cellular processes. Numerous data are generalized on the role of CAP1 in the regulation of actin cytoskeleton and its interactions with many actin-binding proteins. Attention is drawn to the similarity of the structure of CAP1 and its contribution to the remodeling of actin filaments in prokaryotes and eukaryotes, as well as to the difference in the interaction of CAP1 with adenylyl cyclase in these cells. In addition, we discuss the participation of CAP1 in various pathological processes.
Assuntos
Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Animais , HumanosRESUMO
Antitumor effects of glycolysis inhibitors monoiodoacetate and 2-deoxyglucose were studied on Lewis lung carcinoma model. Monoiodoacetate exhibited antitumor and antimetastatic activities, being not inferior of methotrexate (reference drug); however, the preparation also demonstrated high systemic toxicity. 2-Deoxyglucose exhibited only antitumor effect, while its antimetastatic activity did not differ from the result in the group without treatment.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Desoxiglucose/farmacologia , Glicólise/efeitos dos fármacos , Ácido Iodoacético/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Linfática/prevenção & controle , Masculino , Metotrexato/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
We studied reception of sex steroid hormones in the tissues of thyroid papillary cancer and benign tumor. Enhanced expression of AR and ERß mRNA reflected malignant tumor growth. Nuclear factors Brn-3α and TRIM16 modulating expression of steroid hormones play an important role in the development of thyroid tumors. It was found that the level of TRIM16 mRNA is associated with the expression of ERß, which seems to be mediated by its antiestrogen effect.
Assuntos
Proteínas de Ligação a DNA/genética , Receptor beta de Estrogênio/genética , Regulação Neoplásica da Expressão Gênica , Receptores Androgênicos/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Fator de Transcrição Brn-3A/genética , Fatores de Transcrição/genética , Adulto , Idoso , Estudos de Casos e Controles , Proteínas de Ligação a DNA/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Transdução de Sinais , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Fator de Transcrição Brn-3A/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido , Ubiquitina-Proteína LigasesRESUMO
Chymotrypsin- and caspase-like activities and expression of the total proteasome pool subunits (α1α2α3α5α6α7) were studied in patients with non-small-cell lung cancer. Proteasome activities were higher in the primary tumors and lymphogenic metastases than in corresponding adjacent lung tissue. The content of α1α2α3α5α6α7 subunits decreased in metastases and remained unchanged in primary tumor tissue. The development of metastatic process in non-small-cell lung cancer was associated with nonlinear changes in proteasome activities and content in primary tumor tissue and lymphogenic metastases.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Feminino , Humanos , Técnicas In Vitro , Metástase Linfática , Masculino , Pessoa de Meia-IdadeRESUMO
The model of head and neck squamous cell carcinoma (HNSCC) was used to study the expression of genes encoding actin-binding proteins depending on the type of cell motility. The expression of SNAIL1 and CAPN2 mRNA in HNSCC tissue was higher than in specimens of dysplastic epithelium of the larynx and hypopharynx, which can be explained by activation of mesenchymal and amoeboid types of cell motility. In biopsy material of HNSCC patients with T1-2N0M0, expression of genes responsible for actin-binding proteins differed from that of patients with pretumor pathology of the larynx and hypopharynx: expression of FSCN was lower, while expressions of EZR and CAP1 were higher. The data attest that progression of HNSCC is associated with activation of both types of cell motility and with the changes in the expression of mRNA encoding cell motility proteins.
Assuntos
Calpaína/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Fatores de Transcrição da Família Snail/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Calpaína/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Cofilina 1/genética , Cofilina 1/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Progressão da Doença , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hipofaringe/metabolismo , Hipofaringe/patologia , Laringe/metabolismo , Laringe/patologia , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Profilinas/genética , Profilinas/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Vimentina/genética , Vimentina/metabolismo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismoRESUMO
Here, we have investigated the participation of nuclear factors NF-kB, HIF-1 and HIF-2, VEGF, VEGFR2, and carboanhydrase IX in clear-cell renal cancer. We have determined the expression and protein level of transcription factors, VEGF, VEGFR2, and carboanhydrase IX in tumor and normal tissues of 30 patients with kidney cancer. The Real-Time PCR and ELISA were used in the study. The low levels of HIF-1 mRNA expression associated with high levels of HIF-1 protein were also associated with metastasis. The expression levels of VEGF, VEGFR2, and their protein levels are increased in primary tumors of patients with disseminated kidney cancer compared to nonmetastatic cancer. No correlation was revealed between the content of mRNA and encoded proteins in the kidney cancer tissues. The changes in the ratios of mRNA levels and the respective proteins (HIF-1α, HIF-2, NF-kB, VEGF, VEGFR2, and carboanhydrase IX) may contribute to kidney-cancer metastasis.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação Neoplásica da Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/metabolismo , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Metástase Neoplásica , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
Increased proteasome activity was revealed in blood serum of patients with stage T1N0M0 head and neck squamous cell carcinoma in comparison with patients with chronic diseases of the larynx and laryngopharynx. This opens prospects of using chymotrypsin-like activity measurement for differential diagnosis of squamous cell carcinoma, screening for high-risk groups, and evaluation of the degree of tumor differentiation.