Dominance of wild-type p53-mediated transcriptional activation in breast epithelial cells.

Published

Journal Article

The p53 gene is a recessive oncogene whose loss of function can result in cell transformation. Approximately 25% of human breast cancers contain missense mutations in one p53 allele, leading to inactivation of the mutated protein. In almost all of these cases, the wild-type allele is also lost. However, it remains uncertain whether mutant p53 acts in a dominant negative fashion over the wild-type protein. Two parameters of p53 function, transcriptional activation and transcriptional repression, were studied under a variety of experimental conditions within malignant and normal breast epithelial cells. Transient transfection of DNA encoding wild-type p53 was able to transactivate p53-responsive promoters. Wild-type p53 functioned equally well in malignant cells which harbored an endogenous mutation in p53, in malignant cells containing normal p53 and in normal mammary epithelial cells. Co-transfection of cDNAs encoding mutant p53 proteins were unable to inhibit the ability of wild-type p53 to transactivate the reporter constructs. Repression of viral promoters by normal p53 protein was not inhibited by endogenous or co-transfected mutant p53 -proteins. Finally, the p53 regulated gene WAF1/CIP1/p21 was induced following gamma irradiation in normal mammary cells, containing endogenous wild-type p53 and in the same cells transfected with mutant p53 genes. From these experiments we conclude that mutant p53 proteins do not inactivate the transactivating (or repressing) function of a co-expressed normal p53 protein in these cells implying that complete loss of wild-type p53 is required to eliminate these functions in breast epithelium.

Full Text

Duke Authors

Cited Authors

  • Davis, P; Bazar, K; Huper, G; Lozano, G; Marks, J; Iglehart, JD

Published Date

  • September 1996

Published In

Volume / Issue

  • 13 / 6

Start / End Page

  • 1315 - 1322

PubMed ID

  • 8808706

Pubmed Central ID

  • 8808706

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

International Standard Serial Number (ISSN)

  • 0950-9232

Language

  • eng