Abrogation of apoptosis induced by DNA-damaging agents in human bladder-cancer cell lines with p21/WAF1/CIP1 and/or p53 gene alterations
✍ Scribed by Takashi Kawasaki; Yoshihiko Tomita; Vladimir Bilim; Masayuki Takeda; Kota Takahashi; Toshiro Kumanishi
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 570 KB
- Volume
- 68
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The p53-inducible cyclin-dependent kinase inhibitor, p2 I / WAFI/CIPI (p2I), plays a pivotal role in the GI arrest or apoptosis of cells expored to genotoxic stimuli. To determine whether p2 I is a putative tumor-suppressor gene, p2 I status was investigated in 4 human bladder-cancer cell lines of known pi53 status. A pll-gene mutation, one base-pair insertion at codon 20 resulting in a chain-termination change at codon 35, was obsened in one cell line, HT1376, suggesting structural or functional alteration of the p2I protein. When exposed to DNAdamaging agents, cisplatin or mitomycin C, apoptosis was induced in RT4 with the wild-type (wt) p53/wt p21, whereas T24 with the p53 non-sense mutation/wt p2 I was resistant. Of the other 2 cell lines with the p53 mis-sense mutation, apoptosis was induced in SCaBER with the wt p2 I, but HTI 376 with the p2l frame-shift mutation was fairly resistant. These findings suggest that not only p53 alteration, but also p2 I alteration, is important to prevent apoptosis induced by DNA-damaging agents. When exposed to these agents, p53 and p2 I expression was increased in RT4, and not induced in T24. p53 was not induced, but p2 I expression was increased in SCaBER, whereas p53 expression was increased but p l I expression was absent in H T I 376. Thus, p l I expression itself may have an important role in the induction of apoptosis by DNA-damaging agents.