This Article Full Text Full Text (PDF) 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 Lapointe, J. Articles by Labrie, C. Search for Related Content PubMed PubMed Citation Articles by Lapointe, J. Articles by Labrie, C.

Role of the Cyclin-Dependent Kinase Inhibitor p27^Kip1 in Androgen-Induced Inhibition of CAMA-1 Breast Cancer Cell Proliferation

Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Laval University, Québec, Canada G1V 4G2

Address all correspondence and requests for reprints to: Dr. Claude Labrie, Oncology and Molecular Endocrinology Research Center, CHUL Research Center, 2705 Laurier Boulevard, Québec, Québec, Canada G1V 4G2. E-mail: claude.labrie{at}crchul.ulaval.ca

Androgens are known to inhibit the growth of breast cancer cells, but the molecular mechanism of androgen-induced growth inhibition remains unknown. To address this question, we examined functional and quantitative alterations in cell cycle regulators in the E-responsive CAMA-1 breast cancer cell line. We report here that the androgen 5-dihydrotestosterone inhibits the proliferation of CAMA-1 breast cancer cells. This inhibition of cell proliferation was dose dependent, and maximal inhibition of E2-stimulated proliferation was observed at the concentration of 1 nM 5-dihydrotestosterone. 5-Dihydrotestosterone-induced growth arrest was accompanied by an increase in the proportion of cells in the G₁ phase of the cell cycle. Compared with control cells, 5-dihydrotestosterone-treated cells showed an increase in the relative proportion of hypophosphorylated retinoblastoma protein consistent with G₁ arrest. In CAMA-1 cells, 5-dihydrotestosterone caused an accumulation of the cyclin-dependent kinase inhibitor p27^Kip1. Cyclin E-cyclin-dependent kinase-2-associated kinase activity was strongly inhibited in 5-dihydrotestosterone-treated cells, and immunoprecipitation-Western blot analysis showed an increase in the amount of p27^Kip1 associated with cyclin E-cyclin-dependent kinase-2 complexes. These results suggest that inhibition of breast cancer cell growth by androgens may be mediated at least in part by inactivation of the cyclin E-cyclin-dependent kinase-2 complexes by p27^Kip1.

This article has been cited by other articles:

				R. Shibuya, T. Suzuki, Y. Miki, K. Yoshida, T. Moriya, K. Ono, J.-i. Akahira, T. Ishida, H. Hirakawa, D. B Evans, et al. Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast Endocr. Relat. Cancer, March 1, 2008; 15(1): 113 - 124. [Abstract] [Full Text] [PDF]

				J. P Wiebe Progesterone metabolites in breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 717 - 738. [Abstract] [Full Text] [PDF]

				T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, and H. Sasano Sex steroid-producing enzymes in human breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 701 - 720. [Abstract] [Full Text] [PDF]

				J.-L. Carsol, S. Gingras, and J. Simard Synergistic Action of Prolactin (PRL) and Androgen on PRL-Inducible Protein Gene Expression in Human Breast Cancer Cells: A Unique Model for Functional Cooperation between Signal Transducer and Activator of Transcription-5 and Androgen Receptor Mol. Endocrinol., July 1, 2002; 16(7): 1696 - 1710. [Abstract] [Full Text] [PDF]