| First Author | Lain AR | Year | 2013 |
| Journal | Mol Endocrinol | Volume | 27 |
| Issue | 10 | Pages | 1743-61 |
| PubMed ID | 23979845 | Mgi Jnum | J:210714 |
| Mgi Id | MGI:5571692 | Doi | 10.1210/me.2013-1144 |
| Citation | Lain AR, et al. (2013) Research resource: progesterone receptor targetome underlying mammary gland branching morphogenesis. Mol Endocrinol 27(10):1743-61 |
| abstractText | Progesterone (P4)-activated progesterone receptors (PRs) play an essential role in driving pregnancy-associated mammary ductal side-branching morphogenesis and alveologenesis. However, the global cistromic and transcriptome responses that are required to elicit P4-dependent branching morphogenesis have not been elucidated. By combining chromatin immunoprecipitation followed by deep sequencing to identify genome-wide PR-binding sites in PR-positive luminal epithelial cells with global gene expression signatures acutely regulated by PRs in the mammary gland, we have identified a mammary epithelial PR targetome associated with active P4-dependent branching morphogenesis in vivo. We demonstrate that P4-induced side-branching is initiated by epithelial cell rearrangement into a multilayered epithelium that sprouts laterally from quiescent ducts via a mechanism requiring P4-dependent activation of Rac-GTPase signaling. We identify effectors of Rac-GTPases as direct transcriptional targets of PRs, and we demonstrate that disruption of the P4-activated Rac-GTPase signaling axis is sufficient to eliminate P4-dependent side-branching. Our data reveal that the molecular mediators of P4-dependent ductal side-branching overlap with those implicated in breast cancer. |
