Abstract 3380: Transient Tgfβ exposure causes persistent transdifferentiation in mouse mammary epithelial cells in vitro and in vivo

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Transforming growth factor beta (Tgfβ) is transiently increased during involution in the mammary gland following a pregnancy and may promote the risk of pregnancy associated breast cancer (PABC). While tgfβ inhibits growth of normal mammary epithelium and has a functional role in restoring the pre-pregnancy architecture of the mammary gland, this cytokine also has tumor promoter function because it promotes epithelial to mesenchymal transition (EMT) and initiates metastatic behavior in tumor cells. We hypothesize that transient Tgfβ exposure, to mimic involution, selects for cells that are susceptible to EMT and increases risk for PABC. We have found that short term 14 day treatment of CDβGeo cells, a mouse mammary epithelial cell line, with Tgfβ (5ng/ml) promotes EMT. These cells are persistently transdifferentiated (pTD) even after withdrawal of Tgfβ. In contrast to the parental CDβGeo cells, the pTD cells have decreased expression of E-cadherin (3-fold, p 3-fold, p 5-fold;p<0.01). In addition, expression of Tgfb2 mRNA was also increased (2.8-fold;p<0.05) in the pTD cells. These results demonstrate that transient exposure to Tgfβ causes persistent transdifferentation with increases in Snail and Tgfb2 expression in CDβGeo cells and suggest maintenance of transdifferentiation through an autocrine positive feedback loop. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3380. doi:10.1158/1538-7445.AM2011-3380