| First Author | Hatcher RJ | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 3 | Pages | 1008-13 |
| PubMed ID | 24395789 | Mgi Jnum | J:206473 |
| Mgi Id | MGI:5550325 | Doi | 10.1073/pnas.1318124111 |
| Citation | Hatcher RJ, et al. (2014) Pttg1/securin is required for the branching morphogenesis of the mammary gland and suppresses mammary tumorigenesis. Proc Natl Acad Sci U S A 111(3):1008-13 |
| abstractText | Pituitary tumor transforming gene 1 (Pttg1) encodes the mammalian securin, which is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis). PTTG1 is overexpressed in a number of human cancers and has been suggested to be an oncogene. However, we found that, in Pttg1-mutant females, the mammary epithelial cells showed increased proliferation and precocious branching morphogenesis. In accord with these phenotypic changes, progesterone receptor, cyclin D1, and Mmp2 were up-regulated whereas p21 (Cdkn1a) was down-regulated. These molecular changes provide explanation for the observed developmental defects, and suggest that Pttg1 is a tumor suppressor. Indeed, mice lacking Pttg1 developed spontaneous mammary tumors. Furthermore, in human breast tumors, PTTG1 protein levels were down-regulated and the reduction was significantly correlated with the tumor grade. |
