References
Query Results -- Details
MGI Accession ID: MGI:4353843
J Number: J:151417
Other Accession IDs:
Title: A functional connection between pRB and transforming growth factor beta in growth inhibition and mammary gland development.
Authors: Francis SM; Bergsied J; Isaac CE; Coschi CH; Martens AL; Hojilla CV; Chakrabarti S; Dimattia GE; Khoka R; Wang JY; Dick FA
Journal: Mol Cell Biol
Volume: 29
Issue: 16
Date: 2009 Aug
Year: 2009
Pages: 4455-66
Review Status: Peer Reviewed
Abstract:
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.
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