Retrovirally mediated wild-type p53 restores S-phase modulation without inducing WAF1 mRNA in breast carcinoma cells containing mutant p53
✍ Scribed by Dr. Ingo B. Runnebaum; Shan Wang; Rolf Kreienberg
- Book ID
- 102878922
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 767 KB
- Volume
- 59
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
The mechanism of negative growth regulation by the nuclear phosphoprotein p53 in breast cancer cells may rely on its role as a transcriptional activator of cell cycle-related genes. We have tested this hypothesis using retrovirally transduced wild-type (wt) p53 in breast cancer cell lines containing homozygously endogenous mutant (mt) p53. Restoring the expression of wt p53, the percentage of cells in S phase was reduced, G I /S transition was slowed, and progression through S was restrained. The fraction of cells with a flattened "Cdk-minus" phenotype increased 5-to 10-fold. High constitutive mRNA expression of the cyclin-Cdk inhibitor WAF? in MDAMB231 cells was not induced upon restored wt p53 expression suggesting a p53-independent pathway in the regulation of WAF7 mRNA expression. Wt p53 acted trans-dominantly in the presence of accumulating mt p53 and installed a modulation of G I /S transition and S phase progression independent of WAFl expression.