| First Author | Ewan KB | Year | 2005 |
| Journal | Am J Pathol | Volume | 167 |
| Issue | 2 | Pages | 409-17 |
| PubMed ID | 16049327 | Mgi Jnum | J:99950 |
| Mgi Id | MGI:3584291 | Doi | 10.1016/s0002-9440(10)62985-9 |
| Citation | Ewan KB, et al. (2005) Proliferation of Estrogen Receptor-{alpha}-Positive Mammary Epithelial Cells Is Restrained by Transforming Growth Factor-{beta}1 in Adult Mice. Am J Pathol 167(2):409-17 |
| abstractText | Transforming growth factor (TGF)-beta1 is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor (ER)-alpha cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF-beta1 is necessary for the quiescence of ER-alpha-positive populations, we examined mouse mammary epithelial glands at estrus. Approximately 35% of epithelial cells showed TGF-beta1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF-beta signaling is autocrine. Nuclear Smad co-localized with nuclear ER-alpha. To test whether TGF-beta inhibits proliferation, we examined genetically engineered mice with different levels of TGF-beta1. ER-alpha co-localization with markers of proliferation (ie, Ki-67 or bromodeoxyuridine) at estrus was significantly increased in the mammary glands of Tgfbeta1 C57/bl/129SV heterozygote mice. This relationship was maintained after pregnancy but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF-beta1 via the MMTV promoter suppressed proliferation of ER-alpha-positive cells. Thus, TGF-beta1 activation functionally restrains ER-alpha-positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF-beta1 dysregulation may promote proliferation of ER-alpha-positive cells associated with breast cancer risk in humans. |
