dc.contributor.author | Ewan, Kenneth BR | |
dc.contributor.author | Oketch-Rabah, Hellen A | |
dc.contributor.author | Ravani, Shraddha A | |
dc.contributor.author | Shyamala, G | |
dc.contributor.author | Moses, Harold L | |
dc.contributor.author | Barcellos-Hoff, Mary Helen | |
dc.date.accessioned | 2015-06-24T12:36:16Z | |
dc.date.available | 2015-06-24T12:36:16Z | |
dc.date.issued | 2005 | |
dc.identifier.citation | The American Journal of Pathology Volume 167, Issue 2, August 2005, Pages 409–417 | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/pii/S0002944010629859 | |
dc.identifier.uri | http://hdl.handle.net/11295/85582 | |
dc.description.abstract | Transforming growth factor (TGF)-β1 is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor (ER)-α cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF-β1 is necessary for the quiescence of ER-α-positive populations, we examined mouse mammary epithelial glands at estrus. Approximately 35% of epithelial cells showed TGF-β1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF-β signaling is autocrine. Nuclear Smad co-localized with nuclear ER-α. To test whether TGF-β inhibits proliferation, we examined genetically engineered mice with different levels of TGF-β1. ER-α co-localization with markers of proliferation (ie, Ki-67 or bromodeoxyuridine) at estrus was significantly increased in the mammary glands of Tgfβ1 C57/bl/129SV heterozygote mice. This relationship was maintained after pregnancy but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF-β1 via the MMTV promoter suppressed proliferation of ER-α-positive cells. Thus, TGF-β1 activation functionally restrains ER-α-positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF-β1 dysregulation may promote proliferation of ER-α-positive cells associated with breast cancer risk in humans. | en_US |
dc.language.iso | en | en_US |
dc.title | Proliferation of estrogen receptor-α-positive mammary epithelial cells is restrained by transforming growth factor-β1 in adult mice | en_US |
dc.type | Article | en_US |
dc.type.material | en | en_US |