p53-Dependent and -independent responses to cisplatin in mouse testicular teratocarcinoma cells.

Abstract

Testicular cancers respond favorably to chemotherapy with the platinum-containing drug cis-diamminedichloroplatinum(II) (cisplatin). One factor that could explain the efficacy of cisplatin is the low frequency of p53 mutations observed in this tumor type. The present study examines the p53-mediated responses in murine testicular teratocarcinoma cells exposed to the drug. Cisplatin treatment of teratocarcinoma cells with a wild-type p53 gene resulted in accumulation of the p53 protein through posttranscriptional mechanisms; induction of p53-target genes was also observed. Drug treatment resulted in rapid apoptosis in p53-wild-type cells but not in p53(-/-) teratocarcinoma cells. In the latter cells, cisplatin exposure caused prolonged cell cycle arrest accompanied by induction of the p21 gene. Clonogenic assays demonstrated that the p53 mutation did not confer resistance to cisplatin. These experiments suggest that cisplatin inhibits cellular proliferation of testicular teratocarcinoma cells by two possible mechanisms, p53-dependent apoptosis and p53-independent cell cycle arrest.

• Authors: D B Zamble, T Jacks, S J Lippard
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 95 Issue 11 Pg. 6163-8 (May 26 1998) ISSN: 0027-8424 [Print] United States
• PMID: 9600935 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Tumor Suppressor Protein p53
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cisplatin (pharmacology, therapeutic use)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genes, p53
• Male
• Mice
• Mutation
• Neoplasms, Experimental (drug therapy, genetics, metabolism)
• Teratocarcinoma (drug therapy, genetics, metabolism)
• Testicular Neoplasms (drug therapy, genetics, metabolism)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (genetics, metabolism)