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Increased expression of cyclin D1 in a murine mammary epithelial cell line induces p27(kip1), inhibits growth, and enhances apoptosis
Author(s): Han EKH, Begemann M, Sgambato A, Soh JW, Doki Y, Xing WQ, Liu W, Weinstein IB
Source: CELL GROWTH & DIFFERENTIATION    Volume: 7    Issue: 6    Pages: 699-710    Published: JUN 1996  
Times Cited: 122     References: 121     
Abstract: Cyclin D1 is frequently amplified and/or overexpressed in human breast cancer and several other types of cancer. To examine the role of cyclin D1 in normal mammary epithelial cells, in the present study we have overexpressed human cyclin D1 in the mouse mammary epithelial cell line HC11, using retrovirus-mediated transduction. We found that the cyclin D1 overexpresser clones displayed a decrease in saturation density, a decrease in anchorage-independent growth, an increased fraction of cells in the G(0)-G(1) phase, and increased expression of beta-casein, when compared to the control cells, The latter finding suggested that they were more differentiated. Furthermore, the cyclin D1 overexpressers displayed a marked increase in susceptibility to induction of apoptosis by serum withdrawal or by treatment with hydroxyurea or the protein kinase C inhibitors CGP 41251 and Ro31-8220. Thus, in some mammary epithelial cells, increased expression of cyclin D1 can inhibit growth, induce differentiation, and enhance apoptosis. These effects might be due, at least in part, to the fact that these derivatives displayed increased expression of the p27(kip1) inhibitory protein.
Document Type: Review
Language: English
Addresses:
1. COLUMBIA UNIV COLL PHYS & SURG, COLUMBIA PRESBYTERIAN MED CTR, NEW YORK, NY 10032 USA
2. COLUMBIA UNIV COLL PHYS & SURG, CANC RES INST, NEW YORK, NY 10032 USA
Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106
Subject Category: Cell Biology
IDS Number: UP341
ISSN: 1044-9523
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