Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells.
We were the first to identify cyclin A1 as a p53-induced gene by cDNA expression profiling of p53-sensitive and -resistant tumor cells [Maxwell S. A. and Davis G. E. (2000) Proc. Natl. Acad. Sci. USA 97, 13009-13014]. We show here that cyclin A1 can induce G2 cell cycle arrest, polyploidy, apoptosis, and mitotic catastrophe in H1299 non-small cell lung, TOV-21G ovarian, or 786-0 renal carcinoma cells. More cdk1 protein and kinase activities were observed in cyclin A1-induced cells than in GFP control-induced cells. Thus, cyclin A1 might mediate apoptosis and mitotic catastrophe through an unscheduled or inappropriate activation of cdk1. Two primary renal cell carcinomas expressing mutated p53 exhibited reduced or absent expression of cyclin A1 relative to the corresponding normal tissue. Moreover, renal carcinoma-derived mutant p53s were deficient in inducing cyclin A1 expression in p53-null cells. Cyclin A1 but not cyclin A2 was upregulated in etoposide-treated tumor cells undergoing p53-dependent apoptosis and mitotic catastrophe. Forced upregulation of cyclin A2 did not induce apoptosis. The data implicate cyclin A1 as a downstream player in p53-dependent apoptosis and G2 arrest.
Rivera
A
A
Department of Pathology and Laboratory Medicine, Texas A & M University System Health Science Center, Rm. 252, College Station, 77843-1114, USA.
Mavila
A
A
Bayless
K J
KJ
Davis
G E
GE
Maxwell
S A
SA
D017209:Apoptosis; D016203:CDC2 Protein Kinase / Q000378:metabolism; D019925:Cyclin A / Q000235:genetics* / Q000378:metabolism; D056750:Cyclin A1; D056751:Cyclin A2; D004273:DNA, Neoplasm / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D016195:G2 Phase; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011123:Polyploidy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
C503745:CCNA1 protein, human; C503721:CCNA2 protein, human; D019925:Cyclin A; D056750:Cyclin A1; D056751:Cyclin A2; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D016203:CDC2 Protein Kinase