p53 expression overcomes p21WAF1/CIP1-mediated G1 arrest and induces apoptosis in human cancer cells.

摘要: The p21WAF1/CIP1 gene, which encodes a cyclin-dependent kinase inhibitor, may be critical for tumor suppressor gene p53-induced cell cycle arrest. p53 is known to regulate G1 checkpoint, can either induce arrest or initiate apoptosis. To directly examine the role of in control function, we have introduced human into p53-deficient non-small lung cancer line H1299 using p21WAF1/CIP1-expressing adenoviral vector (AdCMVp21). Infection with AdCMVp21 resulted high levels expression and significantly suppressed growth cells through cycle. In contrast, transient wild-type by recombinant (AdCMVp53) induced apoptotic death rapid loss viability. We then examined effects combined infection AdCMVp53 on explore dominant function these molecules. Interestingly, introduction exogenous overcame p21WAF1/CIP1-mediated at apoptosis, although viral-transduced level was unaffected. These observations suggest that converts result repeated two additional colon adenocarcinoma lines different status, mutant p53-expressing DLD-1 LoVo, suggesting this phemonenon general event among cells. Thus, p53-mediated pathway over pathway, indicating an essential upstream mediator regulation process leading suicide.