Constitutive overexpression of cyclin D1 in human breast epithelial cells does not prevent G1 arrest induced by deprivation of epidermal growth factor.
Non-transformed human breast epithelial cell line MCF10A is dependent on exogenous epidermal growth factor (EGF) for continued growth. Complete G1 arrest was rapidly induced following EGF deprivation. The cell cycle arrest was accompanied by increased levels of p27KIP1, a cyclin-dependent kinase inhibitor, and reduced level of cyclin D1. This was associated with strong inhibition of cyclin-dependent kinase 2 and cyclin D1-associated kinase activities. Introduction of exogenous cyclin D1 into MCF10A (MCF10AD1) cells resulted in an accelerated cell growth rate but did not confer colony-forming capacity. Cell cycle arrest was still achieved in MCF10AD1 cells following EGF deprivation. In the great majority of MCF10AD1 clones, accumulation in G1 phase was accompanied by reduced cyclin D1 and increased p27KIP1 protein levels. In two clones where cyclin D remained unchanged during G1 arrest, it was found that more cyclin D1 protein was bound to p27KIP1. The data demonstrate that ectopic expression of cyclin D1 alone could not transform MCF10A cells nor was it sufficient to prevent G1 arrest induced by EGF deprivation.
Chou
J L
JL
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Fan
Z
Z
DeBlasio
T
T
Koff
A
A
Rosen
N
N
Mendelsohn
J
J
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001940:Breast / Q000166:cytology* / Q000378:metabolism*; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000494:pharmacology; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000172:deficiency*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases