Recent advancements in mammary gland biology demonstrate conflicting models in maintenance of basal and luminal cell compartments by either unipotent or bipotent mammary stem cells. However, the molecular mechanisms underlying control of the basal cell compartment, including stem cells, remain poorly understood. Here we explore the currently unknown transcriptional mechanisms of basal stem cell (BSC) maintenance, in addition to addressing the role of the basal cell compartment in preserving luminal cell fate and promoting development of human breast tumors of luminal origin. We discover a novel function for the Co-factor of LIM domains (Clim) transcriptional regulator in promoting mammary gland branching morphogenesis and breast tumorigenesis through maintenance of the basal stem cell population. The transcriptional networks coordinated by Clims in basal mammary epithelial cells also preserve the identity of luminal epithelial cells, demonstrating a crosstalk between these two cellular compartments. Furthermore, we correlate developmental gene expression data with human breast cancer to investigate the role of developmental pathways during the initiation and progression of breast cancer. The gene regulatory networks identified during development, including those specifically coordinated by Clims, correlate with breast cancer patient outcome, suggesting these genes play an important role in the progression of breast cancer.
Vyšlo v časopise: The Co-factor of LIM Domains (CLIM/LDB/NLI) Maintains Basal Mammary Epithelial Stem Cells and Promotes Breast Tumorigenesis. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004520 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004520
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