Mutant p53-induced immortalization of primary human mammary epithelial cells

Qingshen Gao, Stephen H. Hauser, Xiao Long Liu, David E. Wazer, Hywell Madoc-Jones, Vimla Band

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Abstract

Mutations of the p53 gene are the most frequent genetic lesions in breast cancer, suggesting a critical rule for p53 protein in normal mammary cell growth control. Indeed, the p53-targeting human papillomavirus oncogene E6 induces efficient immortalization of normal human mammary epithelial cells (MECs). To assess whether selective loss of p53 is sufficient for MEC immortalization, we introduced seven missense mutants and one single-amino acid deletion mutant (del239) of p53 into the 76N normal MEC strain. Although the missense mutuals failed to immortalize MECs, the del239 mutant reproducibly immortalized these cells. The immortal cells were anchorage dependent and nontumorigenic, indicating a preneoplastic transformation. γ- Irradiation of these cells failed to induce G1 cell cycle arrest and did not lead to an increase in WAF1 and mdm-2 mRNA levels, demonstrating a loss of the endogenous p53 function. These results demonstrate that selective ablation of p53 function by a dominant-negative mutant is sufficient for immortalization of MECs. Availability of an immortalizing as well as several nonimmortalizing p53 mutants should help identify functions critical for cell growth control by p53 in mammary epithelial cells.

Original languageEnglish (US)
Pages (from-to)3129-3133
Number of pages5
JournalCancer Research
Volume56
Issue number13
Publication statusPublished - Jul 1 1996

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gao, Q., Hauser, S. H., Liu, X. L., Wazer, D. E., Madoc-Jones, H., & Band, V. (1996). Mutant p53-induced immortalization of primary human mammary epithelial cells. Cancer Research, 56(13), 3129-3133.