This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davison, E. A. Articles by Musgrove, E. A. Search for Related Content PubMed PubMed Citation Articles by Davison, E. A. Articles by Musgrove, E. A.

The Cyclin-Dependent Kinase Inhibitor p27 (Kip1) Regulates Both DNA Synthesis and Apoptosis in Mammary Epithelium But Is Not Required for Its Functional Development during Pregnancy

Cancer Research Program (E.A.D., C.S.L.L., M.J.N., S.R.O., R.L.S., C.J.O., E.A.M.), Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, New South Wales 2010, Australia; and Laboratory of Genetics and Physiology (L.H.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0822

Address all correspondence and requests for reprints to: Elizabeth A. Musgrove, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail: e.musgrove{at}garvan.org.au.

Decreased expression of the cyclin-dependent kinase (CDK) inhibitor p27(Kip1) is common in breast cancer and is associated with poor prognosis. p27 is also an important mediator of steroidal regulation of cell cycle progression. We have therefore investigated the role of p27 in mammary epithelial cell proliferation. Examination of the two major functions of p27, assembly of cyclin D1-Cdk4 complexes and inhibition of Cdk2 activity, revealed that cyclin D1-Cdk4 complex formation was not impaired in p27^-/- mammary epithelial cells in primary culture. However, cyclin E-Cdk2 activity was increased approximately 3-fold, indicating that the CDK inhibitory function of p27 is important in mammary epithelial cells. Increased epithelial DNA synthesis was observed during pregnancy in p27^-/- mammary gland transplants, but this was paralleled by increased apoptosis. During pregnancy and at parturition, development and differentiation of p27^+/+ and p27^-/- mammary tissue were indistinguishable. These results demonstrate a role for p27 in both the proliferation and survival of mammary epithelial cells. However, the absence of morphological and cellular defects in p27^-/- mammary tissue during pregnancy raises the possibility that loss of p27 in breast cancer may not confer an overall growth advantage unless apoptosis is also impaired.

This article has been cited by other articles:

				C. E. Caldon, A. Swarbrick, C. S.L. Lee, R. L. Sutherland, and E. A. Musgrove The Helix-Loop-Helix Protein Id1 Requires Cyclin D1 to Promote the Proliferation of Mammary Epithelial Cell Acini Cancer Res., April 15, 2008; 68(8): 3026 - 3036. [Abstract] [Full Text] [PDF]

				F. Y. Wu, S. E. Wang, M. E. Sanders, I. Shin, F. Rojo, J. Baselga, and C. L. Arteaga Reduction of Cytosolic p27Kip1 Inhibits Cancer Cell Motility, Survival, and Tumorigenicity Cancer Res., February 15, 2006; 66(4): 2162 - 2172. [Abstract] [Full Text] [PDF]

				B. Chen, H. Pan, L. Zhu, Y. Deng, and J. W. Pollard Progesterone Inhibits the Estrogen-Induced Phosphoinositide 3-Kinase->AKT->GSK-3{beta}->Cyclin D1->pRB Pathway to Block Uterine Epithelial Cell Proliferation Mol. Endocrinol., August 1, 2005; 19(8): 1978 - 1990. [Abstract] [Full Text] [PDF]

				L. K. Pierson-Mullany and C. A. Lange Phosphorylation of Progesterone Receptor Serine 400 Mediates Ligand-Independent Transcriptional Activity in Response to Activation of Cyclin-Dependent Protein Kinase 2 Mol. Cell. Biol., December 15, 2004; 24(24): 10542 - 10557. [Abstract] [Full Text] [PDF]