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Retrovirally mediated wild‐type p53 restores S‐phase modulation without inducing WAF1 mRNA in breast carcinoma cells containing mutant p53
Author(s) -
Runnebaum Ingo B.,
Wang Shan,
Kreienberg Rolf
Publication year - 1995
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240590413
Subject(s) - cyclin dependent kinase , cdk inhibitor , cell cycle , mutant , wild type , biology , cancer research , messenger rna , microbiology and biotechnology , cyclin , chemistry , apoptosis , gene , biochemistry
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, G1/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 WAF1 in MDAMB231 cells was not induced upon restored wt p53 expression suggesting a p53‐independent pathway in the regulation of WAF1 mRNA expression. Wt p53 acted trans‐dominantly in the presence of accumulating mt p53 and installed a modulation of G1/S transition and S phase progression independent of WAF1 expression. © 1995 Wiley‐Liss, Inc.