Suppression of human colorectal carcinoma cell growth by wild-type p53

Suzanne J. Baker, Sanford Markowitz, Eric R. Fearon, James K V Willson, Bert Vogelstein

Research output: Contribution to journalArticle

1517 Citations (Scopus)

Abstract

Mutations of the p53 gene occur commonly in colorectal carcinomas and the wild-type p53 allele is often concomitantly deleted. These findings suggest that the wild-type gene may act as a suppressor of colorectal carcinoma cell growth. To test this hypothesis, wild-type or mutant human p53 genes were transfected into human colorectal carcinoma cell lines. Cells transfected with the wild-type gene formed colonies five- to tenfold less efficiently than those transfected with a mutant p53 gene. In those colonies that did form after wild-type gene transfection, the p53 sequences were found to be deleted or rearranged, or both, and no exogenous p53 messenger RNA expression was observed. In contrast, transfection with the wild-type gene had no apparent effect on the growth of epithelial cells derived from a benign colorectal tumor that had only wild-type p53 alleles. Immunocytochemical techniques demonstrated that carcinoma cells expressing the wild-type gene did not progress through the cell cycle, as evidenced by their failure to incorporate thymidine into DNA. These studies show that the wild-type gene can specifically suppress the growth of human colorectal carcinoma cells in vitro and that an in vivo-derived mutation resulting in a single conservative amino acid substitution in the p53 gene product abrogates this suppressive ability.

Original languageEnglish (US)
Pages (from-to)912-915
Number of pages4
JournalScience
Volume249
Issue number4971
StatePublished - Aug 24 1990

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p53 Genes
Colorectal Neoplasms
Growth
Genes
Transfection
Alleles
Mutation
Amino Acid Substitution
Thymidine
Cell Cycle
Epithelial Cells
Carcinoma
Cell Line
Messenger RNA
DNA

ASJC Scopus subject areas

  • General

Cite this

Baker, S. J., Markowitz, S., Fearon, E. R., Willson, J. K. V., & Vogelstein, B. (1990). Suppression of human colorectal carcinoma cell growth by wild-type p53. Science, 249(4971), 912-915.

Suppression of human colorectal carcinoma cell growth by wild-type p53. / Baker, Suzanne J.; Markowitz, Sanford; Fearon, Eric R.; Willson, James K V; Vogelstein, Bert.

In: Science, Vol. 249, No. 4971, 24.08.1990, p. 912-915.

Research output: Contribution to journalArticle

Baker, SJ, Markowitz, S, Fearon, ER, Willson, JKV & Vogelstein, B 1990, 'Suppression of human colorectal carcinoma cell growth by wild-type p53', Science, vol. 249, no. 4971, pp. 912-915.
Baker SJ, Markowitz S, Fearon ER, Willson JKV, Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912-915.
Baker, Suzanne J. ; Markowitz, Sanford ; Fearon, Eric R. ; Willson, James K V ; Vogelstein, Bert. / Suppression of human colorectal carcinoma cell growth by wild-type p53. In: Science. 1990 ; Vol. 249, No. 4971. pp. 912-915.
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AB - Mutations of the p53 gene occur commonly in colorectal carcinomas and the wild-type p53 allele is often concomitantly deleted. These findings suggest that the wild-type gene may act as a suppressor of colorectal carcinoma cell growth. To test this hypothesis, wild-type or mutant human p53 genes were transfected into human colorectal carcinoma cell lines. Cells transfected with the wild-type gene formed colonies five- to tenfold less efficiently than those transfected with a mutant p53 gene. In those colonies that did form after wild-type gene transfection, the p53 sequences were found to be deleted or rearranged, or both, and no exogenous p53 messenger RNA expression was observed. In contrast, transfection with the wild-type gene had no apparent effect on the growth of epithelial cells derived from a benign colorectal tumor that had only wild-type p53 alleles. Immunocytochemical techniques demonstrated that carcinoma cells expressing the wild-type gene did not progress through the cell cycle, as evidenced by their failure to incorporate thymidine into DNA. These studies show that the wild-type gene can specifically suppress the growth of human colorectal carcinoma cells in vitro and that an in vivo-derived mutation resulting in a single conservative amino acid substitution in the p53 gene product abrogates this suppressive ability.

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