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1.
J Mammary Gland Biol Neoplasia ; 27(3-4): 233-239, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36242657

RESUMO

The thirteenth annual workshop of the European Network for Breast Development and Cancer (ENBDC) Laboratories Annual Workshop took place on the 28-30 April 2022 in Weggis, Switzerland and focused on methods in mammary gland biology and breast cancer. Sixty scientists participated in the ENBDC annual workshop which had not been held in person since 2019 due to the global COVID-19 pandemic. Topics spanned the mammary gland biology field, ranging from lactation biology and embryonic development, single cell sequencing of the human breast, and stunning cutting-edge imaging of the mouse mammary gland and human breast as well as breast cancer research topics including invasive progression of the pre-invasive DCIS stage, metabolic determinants of endocrine therapy resistance, models for lobular breast cancer, and how mutational landscapes of normal breast during age and pregnancy determine cancer risk. The latest findings from participating researchers were presented through oral presentations and poster sessions and included plenty of unpublished work.


Assuntos
Neoplasias da Mama , COVID-19 , Glândulas Mamárias Humanas , Feminino , Camundongos , Animais , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Glândulas Mamárias Humanas/metabolismo , Pandemias , Biologia , Glândulas Mamárias Animais/metabolismo
2.
Methods Mol Biol ; 2471: 221-233, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35175600

RESUMO

The mammary intraductal xenografting technique has been established to inject cells or other substances directly into the mammary ducts of female mice. Using this refined xenografting method provides the possibility of mimicking the normal microenvironment of preinvasive breast lesions including, ductal carcinoma in situ (DCIS), to study of the progression of DCIS to invasive breast cancer in a more relevant manner than with other mammary xenografting methods. Xenografting into the mammary fat pad delivers cells directly into the stroma and bypasses the occurrence of invasive transition, during which cells invade through the basement membrane. Either breast cancer cell lines or patient-derived breast cancer cells can be injected into the mammary duct using this protocol to model breast cancer progression. This protocol will cover the procedures required to perform this technique.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Glândulas Mamárias Animais , Animais , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Feminino , Humanos , Camundongos , Transplante Heterólogo , Microambiente Tumoral
3.
Dis Model Mech ; 14(5)2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33969421

RESUMO

Little is known about the role of Sox11 in the regulation of mammary progenitor cells. Sox11 is expressed by mammary bud epithelial cells during embryonic mammary gland development and is not detected in mammary epithelial cells after birth. As Sox11 is an oncofetal gene, we investigated the effects of reducing Sox11 levels in embryonic mammary progenitor cells and found that Sox11 regulates proliferative state, stem cell activity and lineage marker expression. We also investigated the effect of reducing Sox11 levels in two transplantable Brca1-deficient oestrogen receptor-negative mouse mammary tumour cell lines, to assess whether Sox11 regulates similar functions in tumour progenitor cells. When Sox11 levels were reduced in one Brca1-deficient mammary tumour cell line that expressed both epithelial and mesenchymal markers, similar effects on proliferation, stem cell activity and expression of lineage markers to those seen in the embryonic mammary progenitor cells were observed. Orthotopic grafting of mammary tumour cells with reduced Sox11 levels led to alterations in tumour-initiating capacity, latency, expression of lineage markers and metastatic burden. Our results support a model in which tumours expressing higher levels of Sox11 have more stem and tumour-initiating cells, and are less proliferative, whereas tumours expressing lower levels of Sox11 become more proliferative and capable of morphogenetic/metastatic growth, similar to what occurs during embryonic mammary developmental progression.


Assuntos
Proteína BRCA1/deficiência , Carcinogênese/metabolismo , Carcinogênese/patologia , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia , Fatores de Transcrição SOXC/metabolismo , Animais , Proteína BRCA1/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Linhagem da Célula , Proliferação de Células , Sobrevivência Celular , Células-Tronco Embrionárias/metabolismo , Feminino , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/embriologia , Camundongos , Metástase Neoplásica
4.
Elife ; 92020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909943

RESUMO

SOX11 is an embryonic mammary epithelial marker that is normally silenced prior to birth. High SOX11 levels in breast tumours are significantly associated with distant metastasis and poor outcome in breast cancer patients. Here, we show that SOX11 confers distinct features to ER-negative DCIS.com breast cancer cells, leading to populations enriched with highly plastic hybrid epithelial/mesenchymal cells, which display invasive features and alterations in metastatic tropism when xenografted into mice. We found that SOX11+DCIS tumour cells metastasize to brain and bone at greater frequency and to lungs at lower frequency compared to cells with lower SOX11 levels. High levels of SOX11 leads to the expression of markers associated with mesenchymal state and embryonic cellular phenotypes. Our results suggest that SOX11 may be a potential biomarker for breast tumours with elevated risk of developing metastases and may require more aggressive therapies.


Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal/genética , Invasividade Neoplásica/patologia , Fatores de Transcrição SOXC/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Xenoenxertos , Humanos , Camundongos , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/farmacologia
5.
Semin Cancer Biol ; 67(Pt 1): 3-11, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32574812

RESUMO

The transcription factor SOX11 (SRY-related high-mobility-group (HMG) box 11), a member of the SOXC group, is expressed during embryogenesis but largely absent in most adult differentiated tissues. SOX11 regulates progenitor and stem cell behavior, and often acts together with the other two SOXC group members, SOX4 and SOX12, in regulating developmental processes, including neurogenesis and skeletogenesis. Dysregulation of SOX11 has been implicated in a number of diseases including, neurodevelopmental disorders and osteoarthritis, and a wide variety of cancers. Functions of SOX11 during both development and disease could be attributed to its context-dependent post-transcriptional modifications or interaction with other co-factors. We review the molecular and functional roles of SOX11 during development where similar processes appear to be deregulated in cancers.


Assuntos
Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Neoplasias/patologia , Fatores de Transcrição SOXC/metabolismo , Células-Tronco/patologia , Animais , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Fatores de Transcrição SOXC/genética , Células-Tronco/metabolismo
6.
Dis Model Mech ; 13(7)2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32493768

RESUMO

SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here, we present a comprehensive mouse reference spectral library (MouseRefSWATH) that permits quantification of up to 10,597 proteins (62.2% of the mouse proteome) by SWATH-MS. We exploit MouseRefSWATH to develop an analytical pipeline for species-specific deconvolution of proteomic alterations in human tumour xenografts (XenoSWATH). This method overcomes the challenge of high sequence similarity between mouse and human proteins, facilitating the study of host microenvironment-tumour interactions from 'bulk tumour' measurements. We apply the XenoSWATH pipeline to characterize an intraductal xenograft model of breast ductal carcinoma in situ and uncover complex regulation consistent with stromal reprogramming, where the modulation of cell migration pathways is not restricted to tumour cells but also operates in the mouse stroma upon progression to invasive disease. MouseRefSWATH and XenoSWATH open new opportunities for in-depth and reproducible proteomic assessment to address wide-ranging biological questions involving this important model organism.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/metabolismo , Proteínas de Neoplasias/metabolismo , Proteoma , Proteômica , Células Estromais/metabolismo , Espectrometria de Massas em Tandem , Animais , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Comunicação Celular , Linhagem Celular Tumoral , Cromatografia Líquida , Bases de Dados de Proteínas , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos SCID , Células NIH 3T3 , Transplante de Neoplasias , Especificidade da Espécie , Células Estromais/patologia , Microambiente Tumoral
7.
Oncogene ; 38(17): 3151-3169, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30622340

RESUMO

Increased cancer stem cell content during development of resistance to tamoxifen in breast cancer is driven by multiple signals, including Sox2-dependent activation of Wnt signalling. Here, we show that Sox2 increases and estrogen reduces the expression of the transcription factor Sox9. Gain and loss of function assays indicate that Sox9 is implicated in the maintenance of human breast luminal progenitor cells. CRISPR/Cas knockout of Sox9 reduces growth of tamoxifen-resistant breast tumours in vivo. Mechanistically, Sox9 acts downstream of Sox2 to control luminal progenitor cell content and is required for expression of the cancer stem cell marker ALDH1A3 and Wnt signalling activity. Sox9 is elevated in breast cancer patients after endocrine therapy failure. This new regulatory axis highlights the relevance of SOX family transcription factors as potential therapeutic targets in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOX9/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Mama/citologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular , Proliferação de Células , Células Epiteliais/citologia , Estrogênios/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Fatores de Transcrição SOX9/genética , Transdução de Sinais , Tamoxifeno/farmacologia , Regulação para Cima
8.
Commun Biol ; 1: 228, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30564749

RESUMO

Embryonic mammary cells are a unique population comprised of undifferentiated, highly plastic progenitor cells that create normal mammary tissues. The mammary gland continues to develop after birth from descendants of embryonic mammary cells. Here, we establish cell lines from mouse mammary organs, immediately after they formed during prenatal development, to facilitate studies of primitive mammary cells, which are difficult to isolate in sufficient quantities for use in functional experiments. We show that some lines can be induced to secrete milk, a distinguishing feature of mammary epithelial cells. Targeted deletion of Sox9, from one clone, decreases the ability to respond to lactogenic stimuli, consistent with a previously identified role for Sox9 in regulating luminal progenitor function. Sox9 ablation also leads to alterations in 3D morphology and downregulation of Zeb1, a key epithelial-mesenchymal transition regulator. Prenatal mammary cell lines are an invaluable resource to study regulation of mammary progenitor cell biology and development.

9.
Breast Cancer Res ; 20(1): 102, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30180882

RESUMO

The European Network for Breast Development and Cancer (ENBDC), a worldwide network ( http://www.enbdc.org/ ), celebrated its tenth anniversary with a fantastic meeting last March 15-17, 2018 in Weggis with 76 attendees.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Mama/diagnóstico por imagem , Glândulas Mamárias Humanas/diagnóstico por imagem , Pesquisadores/estatística & dados numéricos , Pesquisa Biomédica/métodos , Pesquisa Biomédica/tendências , Feminino , Humanos
10.
Nat Cell Biol ; 20(6): 637-639, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29784916
11.
J Proteomics ; 189: 11-22, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29501709

RESUMO

Proteomic analysis of extracellular matrix (ECM) and ECM-associated proteins, collectively known as the matrisome, is a challenging task due to the inherent complexity and insolubility of these proteins. Here we present sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS) as a tool for the quantitative analysis of matrisomal proteins in both non-enriched and ECM enriched tissue without the need for prior fractionation. Utilising a spectral library containing 201 matrisomal proteins, we compared the performance and reproducibility of SWATH MS over conventional data-dependent analysis mass spectrometry (DDA MS) in unfractionated murine lung and liver. SWATH MS conferred a 15-20% increase in reproducible peptide identification across replicate experiments in both tissue types and identified 54% more matrisomal proteins in the liver versus DDA MS. We further use SWATH MS to evaluate the quantitative changes in matrisome content that accompanies ECM enrichment. Our data shows that ECM enrichment led to a systematic increase in core matrisomal proteins but resulted in significant losses in matrisome-associated proteins including the cathepsins and proteins of the S100 family. Our proof-of-principle study demonstrates the utility of SWATH MS as a versatile tool for in-depth characterisation of the matrisome in unfractionated and non-enriched tissues. SIGNIFICANCE: The matrisome is a complex network of extracellular matrix (ECM) and ECM-associated proteins that provides scaffolding function to tissues and plays important roles in the regulation of fundamental cellular processes. However, due to its inherent complexity and insolubility, proteomic studies of the matrisome typically require the application of enrichment workflows prior to MS analysis. Such enrichment strategies often lead to losses in soluble matrisome-associated components. In this study, we present sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH MS) as a tool for the quantitative analysis of matrisomal proteins. We show that SWATH MS provides a more reproducible coverage of the matrisome compared to data-dependent analysis (DDA) MS. We also demonstrate that SWATH MS is capable of accurate quantification of matrisomal proteins without prior ECM enrichment and fractionation, which may simplify sample handling workflows and avoid losses in matrisome-associated proteins commonly linked to ECM enrichment.


Assuntos
Proteínas da Matriz Extracelular/análise , Matriz Extracelular/metabolismo , Espectrometria de Massas/métodos , Proteoma/análise , Proteômica/métodos , Animais , Fracionamento Químico , Interpretação Estatística de Dados , Matriz Extracelular/química , Proteínas da Matriz Extracelular/metabolismo , Feminino , Camundongos , Camundongos SCID
12.
J Pathol ; 243(2): 193-207, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28707729

RESUMO

Here, we show that SOX11, an embryonic mammary marker that is normally silent in postnatal breast cells, is expressed in many oestrogen receptor-negative preinvasive ductal carcinoma in situ (DCIS) lesions. Mature mammary epithelial cells engineered to express SOX11 showed alterations in progenitor cell populations, including an expanded basal-like population with increased aldehyde dehydrogenase (ALDH) activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 showed increased ALDH activity, which is a feature of cancer stem cells. The CD44+/CD24-/ALDH+ cell population was increased in DCIS.com cells that expressed SOX11. Upregulating SOX11 expression in DCIS.com cells led to increased invasive growth both in vitro and when they were injected intraductally in a mouse model of DCIS that recapitulates human disease. Invasive lesions formed sooner and tumour growth was augmented in vivo, suggesting that SOX11 contributes to the progression of DCIS to invasive breast cancer. We identified potential downstream effectors of SOX11 during both microinvasive and invasive tumour growth stages, including several with established links to regulation of progenitor cell function and prenatal developmental growth. Our findings suggest that SOX11 is a potential biomarker for DCIS lesions containing cells harbouring distinct biological features that are likely to progress to invasive breast cancer. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias da Mama/etiologia , Carcinoma Ductal de Mama/etiologia , Fatores de Transcrição SOXC/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Neoplasias da Mama/fisiopatologia , Carcinoma Ductal de Mama/fisiopatologia , Progressão da Doença , Células Epiteliais , Feminino , Humanos , Glândulas Mamárias Animais , Camundongos SCID , Fatores de Transcrição SOXC/fisiologia , Células-Tronco/fisiologia , Regulação para Cima/fisiologia
13.
Sci Rep ; 7(1): 5049, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28698625

RESUMO

Mammary gland development begins with the appearance of epithelial placodes that invaginate, sprout, and branch to form small arborized trees by birth. The second phase of ductal growth and branching is driven by the highly invasive structures called terminal end buds (TEBs) that form at ductal tips at the onset of puberty. Ectodysplasin (Eda), a tumor necrosis factor-like ligand, is essential for the development of skin appendages including the breast. In mice, Eda regulates mammary placode formation and branching morphogenesis, but the underlying molecular mechanisms are poorly understood. Fibroblast growth factor (Fgf) receptors have a recognized role in mammary ductal development and stem cell maintenance, but the ligands involved are ill-defined. Here we report that Fgf20 is expressed in embryonic mammary glands and is regulated by the Eda pathway. Fgf20 deficiency does not impede mammary gland induction, but compromises mammary bud growth, as well as TEB formation, ductal outgrowth and branching during puberty. We further show that loss of Fgf20 delays formation of Eda-induced supernumerary mammary buds and normalizes the embryonic and postnatal hyperbranching phenotype of Eda overexpressing mice. These findings identify a hitherto unknown function for Fgf20 in mammary budding and branching morphogenesis.


Assuntos
Ectodisplasinas/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Glândulas Mamárias Animais/crescimento & desenvolvimento , Maturidade Sexual , Animais , Proliferação de Células , Feminino , Fatores de Crescimento de Fibroblastos/deficiência , Fatores de Crescimento de Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Glândulas Mamárias Animais/embriologia , Camundongos Endogâmicos C57BL , Fenótipo
14.
Biochem J ; 473(21): 3979-3995, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27589945

RESUMO

The matrisome is a complex and heterogeneous collection of extracellular matrix (ECM) and ECM-associated proteins that play important roles in tissue development and homeostasis. While several strategies for matrisome enrichment have been developed, it is currently unknown how the performance of these different methodologies compares in the proteomic identification of matrisome components across multiple tissue types. In the present study, we perform a comparative proteomic assessment of two widely used decellularisation protocols and two extraction methods to characterise the matrisome in four murine organs (heart, mammary gland, lung and liver). We undertook a systematic evaluation of the performance of the individual methods on protein yield, matrisome enrichment capability and the ability to isolate core matrisome and matrisome-associated components. Our data find that sodium dodecyl sulphate (SDS) decellularisation leads to the highest matrisome enrichment efficiency, while the extraction protocol that comprises chemical and trypsin digestion of the ECM fraction consistently identifies the highest number of matrisomal proteins across all types of tissue examined. Matrisome enrichment had a clear benefit over non-enriched tissue for the comprehensive identification of matrisomal components in murine liver and heart. Strikingly, we find that all four matrisome enrichment methods led to significant losses in the soluble matrisome-associated proteins across all organs. Our findings highlight the multiple factors (including tissue type, matrisome class of interest and desired enrichment purity) that influence the choice of enrichment methodology, and we anticipate that these data will serve as a useful guide for the design of future proteomic studies of the matrisome.


Assuntos
Proteômica/métodos , Animais , Cromatografia Líquida , Eletroforese em Gel de Poliacrilamida , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Espectrometria de Massas em Tandem
15.
Methods Mol Biol ; 1293: 51-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26040680

RESUMO

Embryonic explant culture is a powerful technique to observe tissue morphogenesis ex vivo, and is particularly useful for monitoring embryonic mammary gland development. It has been established that mammary cell lineage specification occurs during embryogenesis, although much remains to be elucidated with respect to how this occurs. During mammary specification, mammary progenitor cells are formed. Embryonic mammary development can proceed and be monitored in embryonic explant culture. Studies using explant culture will greatly enhance our understanding of the cellular mechanisms that regulate embryonic mammary primordial development and mammary progenitor cell specification. We present a protocol for culturing explants from mid-gestation mouse embryos so that morphogenetic processes and mammary epithelial progenitor cells can be studied during embryonic mammary development ex vivo.


Assuntos
Células-Tronco Embrionárias/citologia , Glândulas Mamárias Animais/citologia , Animais , Biomarcadores , Técnicas de Cultura de Células , Separação Celular , Células-Tronco Embrionárias/metabolismo , Feminino , Expressão Gênica , Genes Reporter , Glândulas Mamárias Animais/embriologia , Camundongos , Técnicas de Cultura de Tecidos
16.
Stem Cells Dev ; 23(22): 2758-70, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24936779

RESUMO

Mutation of Neuregulin-3 (Nrg3) results in defective embryonic mammary gland development. Here, we investigate functions of Nrg3 signaling in embryonic mammary morphogenesis. Nrg3 regulates the distribution of epithelial progenitor cells within the presumptive mammary-forming region during early mammary morphogenesis. Basal and suprabasal epithelial cells are significantly smaller within the hypoplastic mammary primordium (MP) that forms in Nrg3 mutants, indicative of failure to acquire mammary epithelial cell (MEC) morphological phenotype. Activation of Erbb4 JM-a CYT-1, an Erbb4 isoform expressed in the developing MP, leads to MEC spreading and migration. Nrg3 promotes the accumulation of epithelial progenitor cells at the MP site in embryo explant cultures. Our results implicate Nrg3 signaling in mediating key events of mammary mesenchyme specification, including mesenchymal condensation, mitosis, and induction of mammary marker expression. Taken together, our results show Nrg3 has a major role in conferring specification of the mammary phenotype to both epithelial and mesenchymal progenitor cells.


Assuntos
Células Epiteliais/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Glândulas Mamárias Animais/fisiologia , Glândulas Mamárias Humanas/fisiologia , Neurregulinas/metabolismo , Células-Tronco/fisiologia , Animais , Diferenciação Celular/fisiologia , Linhagem Celular , Células Epiteliais/metabolismo , Feminino , Humanos , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Humanas/metabolismo , Mesoderma/metabolismo , Mesoderma/fisiologia , Camundongos , Morfogênese/fisiologia , Fenótipo , Isoformas de Proteínas/metabolismo , Receptor ErbB-4/metabolismo , Transdução de Sinais/fisiologia , Células-Tronco/metabolismo
17.
Semin Cell Dev Biol ; 25-26: 43-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24445189

RESUMO

The stroma, which is composed of supporting cells and connective tissue, comprises a large component of the local microenvironment of many epithelial cell types, and influences several fundamental aspects of cell behaviour through both tissue interactions and niche regulation. The significance of the stroma in development and disease has been increasingly recognised. Whereas normal stroma is essential for various developmental processes during vertebrate organogenesis, it can be deregulated and become abnormal, which in turn can initiate or promote a disease process, including cancer. The mouse mammary gland has emerged in recent years as an excellent model system for understanding stromal function in both developmental and cancer biology. Here, we take a systematic approach and focus on the dynamic interactions that the stroma engages with the epithelium during mammary specification, cell differentiation, and branching morphogenesis of both the embryonic and postnatal development of the mammary gland. Similar stromal-epithelial interactions underlie the aetiology of breast cancer, making targeting the cancer stroma an increasingly important and promising therapeutic strategy to pursue for breast cancer treatment.


Assuntos
Mama/embriologia , Mama/crescimento & desenvolvimento , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/crescimento & desenvolvimento , Animais , Mama/citologia , Neoplasias da Mama/patologia , Diferenciação Celular/fisiologia , Células Epiteliais/citologia , Epitélio/embriologia , Epitélio/crescimento & desenvolvimento , Feminino , Humanos , Glândulas Mamárias Animais/citologia , Camundongos , Células Estromais/citologia
18.
J Mammary Gland Biol Neoplasia ; 18(2): 93-104, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23736987

RESUMO

Our understanding of prenatal morphogenesis of mammary glands has recently greatly advanced. This review focuses on morphogenesis proper, as well as cellular processes and tissue interactions involved in the progression of the embryonic mammary gland through sequential morphogenic stages in both the mouse and rabbit embryo. We provide a synthesis of both historical and more recent studies of embryonic mammary gland development, as well as arguments to revise old concepts about mechanisms of mammary line and rudiment formation. Finally, we highlight outstanding issues that remain to be addressed.


Assuntos
Glândulas Mamárias Animais/embriologia , Animais , Feminino , Morfogênese/fisiologia
20.
J Mammary Gland Biol Neoplasia ; 18(2): 227-31, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23649699

RESUMO

Whole-mount immunofluorescent staining facilitates the profiling of protein expression patterns within diverse and complex tissues. Thanks to the application of antibodies on whole mounted instead of sectioned specimens, this technique has many advantages with respect to the preservation of biological and pathological features of specimens when compared to conventional immunohistological methods. Here, we describe a protocol and optimal conditions of whole-mount immunofluorescence for studying the formation of mammary primordia. We also show an example three-dimensional reconstruction of a mammary primordium based on z-stacked images of a whole-mount stained specimen using confocal microscopy and image analysis software.


Assuntos
Imunofluorescência/métodos , Imageamento Tridimensional/métodos , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Humanas/embriologia , Microscopia Confocal/métodos , Animais , Feminino , Humanos , Software
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