Figure 7.
BMP2, which Production Is Induced by Carcinogens, Is Involved in Regulation and Transformation of Human Mammary Stem Cells
(A) ELISA quantification of BMP2 after exposure of peripheral adipose tissue (n = 7), breast adipose tissue (n = 4), breast fibroblasts (n = 6), and stromal cells (n = 9) to 7 Gy irradiation, 10−7 M Bisphenol A/S (BPA/BPS), 10−10 M Benz(a)pyrene (BaP). BMP2 levels are represented as ratios to untreated control ± SEM.
(B and C) Induction of BMP2 expression after 10−7 M BPA treatment of fibroblasts from adipose or breast tissue from healthy donors or breast cancer patients at least 1 year after treatment. Data represent the percentage of patients showing an induction of BMP2 expression quantified by (B) qPCR (healthy donor, n = 15; breast cancer history, n = 10) or (C) ELISA (healthy donor, n = 10; breast cancer history, n = 10).
(D) Proposed mechanism of BMP2 function. In the normal breast, BMP2 commits common progenitors to the luminal lineage, while BMP4 favors the maintenance of immature cells and myoepithelial differentiation. Exposure to environmental carcinogens increases BMP2 levels. Intrinsic alterations of luminal progenitors make the cells susceptible to BMP2 and IL-6-dependent changes of the microenvironment, leading to full transformation. Ad, adipocyte; Fb, fibroblast; SC, stem cell.