| First Author | Williams TM | Year | 2006 |
| Journal | Am J Pathol | Volume | 169 |
| Issue | 5 | Pages | 1784-801 |
| PubMed ID | 17071600 | Mgi Jnum | J:114569 |
| Mgi Id | MGI:3689449 | Doi | 10.2353/ajpath.2006.060590 |
| Citation | Williams TM, et al. (2006) Stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: caveolin-1 antagonizes cyclin d1 function in mammary epithelial cells. Am J Pathol 169(5):1784-801 |
| abstractText | Here, we investigate the role of caveolin-1 (Cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. Cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of Cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. To address this issue, we characterized the development of the mammary ductal system in Cav-1(-/-) mice and performed a series of mammary transplant studies, using both wild-type and Cav-1(-/-) mammary fat pads. Cav-1(-/-) mammary epithelia were hyperproliferative in vivo, with dramatic increases in terminal end bud area and mammary ductal thickness as well as increases in bromodeoxyuridine incorporation, extracellular signal-regulated kinase-1/2 hyperactivation, and up-regulation of STAT5a and cyclin D1. Consistent with these findings, loss of Cav-1 dramatically exacerbated mammary lobulo-alveolar hyperplasia in cyclin D1 Tg mice, whereas overexpression of Cav-1 caused reversion of this phenotype. Most importantly, Cav-1(-/-) mammary stromal cells (fat pads) promoted the growth of both normal mammary ductal epithelia and mammary tumor cells. Thus, Cav-1 expression in both epithelial and stromal cells provides a protective effect against mammary hyperplasia as well as mammary tumorigenesis. |
