p53Val135 temperature sensitive mutant suppresses growth of human breast cancer cells

Daniel Eliyahu, Steve Evans, Neal Rosen, Siona Eliyahu, James Zwiebel, Soonmyoung Paik, Marc Lippman

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

One common step in the malignant progression of a wide variety of human cancers seems to be inactivation of the p53 gene, via point mutation or deletion or both; or overexpression of mutated protein with dominant transforming activity. This study shows a suppressive effect of wild type p53 on the growth of human breast cancer cells. Introduction of wild type p53 versus mutant into five human breast cancer cell lines containing mutant p53 resulted in a marked reduction in colony formation. Two of these were transfected with human wt p53 expression vectors and the other three were infected with retroviruses packaging human wt p53, both showing similar reduction in the number of surviving colonies, suggesting a role for wt p53 in suppression of breast cancer cell growth. Direct evidence for growth suppression was obtained by introduction of the temperature sensitive p53Val135 into Hs578T human breast cancer cells containing a mutant p53. This murine mutant allele p53Val135 functions as an oncogene at 37° C and as a tumor suppressor at 32° C. The cell line generated was strongly growth inhibited at the restrictive temperature (31.5° C), at which temperature the suppressor form is expressed. This inhibition of proliferation was reversible upon a temperature upshift. Analysis of the cell cycle distribution shows these growth suppressed cells to be inhibited in the G1 phase of the cell cycle. Thus wt p53 may have an important role in breast cancer tumorigenesis.

Original languageEnglish (US)
Pages (from-to)167-177
Number of pages11
JournalBreast cancer research and treatment
Volume30
Issue number2
DOIs
StatePublished - Jan 1 1994

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Keywords

  • breast cancer
  • oncogenes
  • p53 transformation
  • temperature sensitive mutant
  • tumor suppressors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Eliyahu, D., Evans, S., Rosen, N., Eliyahu, S., Zwiebel, J., Paik, S., & Lippman, M. (1994). p53Val135 temperature sensitive mutant suppresses growth of human breast cancer cells. Breast cancer research and treatment, 30(2), 167-177. https://doi.org/10.1007/BF00666061