| First Author | Francis SM | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 16 | Pages | 4455-66 |
| PubMed ID | 19506017 | Mgi Jnum | J:151417 |
| Mgi Id | MGI:4353843 | Doi | 10.1128/MCB.00473-09 |
| Citation | Francis SM, et al. (2009) A functional connection between pRB and transforming growth factor beta in growth inhibition and mammary gland development. Mol Cell Biol 29(16):4455-66 |
| abstractText | Transforming growth factor beta (TGF-beta) is a crucial mediator of breast development, and loss of TGF-beta-induced growth arrest is a hallmark of breast cancer. TGF-beta has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-beta cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1(DeltaL) and Rb1(NF)), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-beta growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-beta signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-beta cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-beta in growth control and mammary gland development. |
