Role of p21 in prostaglandin A2-mediated cellular arrest and death.
Prostaglandin A2 (PGA2) treatment induces growth arrest of most cells, and we have recently shown that, for breast carcinoma MCF-7 cells, this is correlated with an induction of the cyclin-dependent kinase inhibitor p21 and reduced cyclin-dependent kinase 2 activity. In this study, we demonstrate that, in RKO cells, PGA2 treatment fails to induce growth arrest, but rather results in significant cell death. These effects are correlated with lack of p21 induction and enhanced cyclin-dependent kinase 2 activity. Reduction of endogenous p21 expression in MCF-7 cells through expression of antisense p21 resulted in a response pattern approaching that seen in RKO cells, characterized by diminished growth arrest and increased death. These findings support a role for p21 in PGA2-mediated growth arrest, which we propose serves to prevent cell death caused by inappropriate cell cycle progression.
Gorospe
M
M
Section on Gene Expression and Aging, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
Holbrook
N J
NJ
D016475:3T3 Cells / Q000166:cytology; D000818:Animals; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000473:pathology; D009374:Neoplasms, Experimental / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C493958:Cdkn1a protein, rat; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016376:Oligonucleotides, Antisense; D011454:Prostaglandins A; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C100008:prostaglandin A2