Increased expression of cyclin D1 in a murine mammary epithelial cell line induces p27kip1, inhibits growth, and enhances apoptosis.
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(zero)-G1 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 p27kip1 inhibitory protein.
Han
E K
EK
Columbia-Presbyterian Cancer Center, Columbia Univerisity, College of Physicians and Surgeons, New York, New York 10032, USA.
Begemann
M
M
Sgambato
A
A
Soh
J W
JW
Doki
Y
Y
Xing
W Q
WQ
Liu
W
W
Weinstein
I B
IB
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D002460:Cell Line; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D006131:Growth Inhibitors / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D015513:Oncogene Proteins / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D025521:Tumor Suppressor Proteins
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D016213:Cyclins; D006131:Growth Inhibitors; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases