Activin B functions downstream of BRCA1 in stem cell maintenance

The cancer stem cell hypothesis proposes that tumors contain a subset of stem or progenitor cells that are resistant to chemotherapy and have evaded the normally tight control of self-renewal. BRCA1 is known to play an essential role in cancer stem cell maintenance and differentiation. In fact, breast tissue from women with germline mutations in BRCA1 show regions of increased ALDH1 positivity, a marker of stem cells. Furthermore, knockdown of BRCA1 in normal tissue from reduction mammoplasty leads to increased ALDH1 and increased stem cell number as assessed by mammosphere formation. Activin B is a secreted protein that is a member of the TGFβ family. It is a homodimer of inhibin βB that is expressed in various tissues and has numerous functions, including regulation of gonadal function, proliferation, metastasis, differentiation and stem cell maintenance.