Research ArticleBREAST CANCER

A TGFβ–miR-182–BRCA1 axis controls the mammary differentiation hierarchy

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Science Signaling  06 Dec 2016:
Vol. 9, Issue 457, pp. ra118
DOI: 10.1126/scisignal.aaf5402

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TGFβ directs mammary lineage

Breast cancers are often be classified by lineage markers for specific cell types, such as the luminal subtype or the relatively more aggressive myoepithelial (also called basal-like) subtype. Mutations in the protein BRCA1 are associated with the basal-like subtype. The growth factor TGFβ suppresses tumorigenesis in various tissues, but malignant mammary epithelial cells have decreased sensitivity to TGFβ. Using mouse models, Martinez-Ruiz et al. found that loss of TGFβ promoted mammary stem cell self-renewal and skewed differentiation to myoepithelial cells through increased abundance of a microRNA (miR-182) that targets and decreases the translation of BRCA1 transcripts. Expressing BRCA1 or blocking miR-182 restored lineage commitment homeostasis in TGFβ-deficient mammary epithelial cells. The findings link two factors in breast cancer development and may have wider implications for tumorigenesis in other epithelial, ductal tissues (such as the colon, pancreas, and prostate) in which BRCA mutations are also a risk factor.

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