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

Science. 1990 Aug 24;249(4971):912-5. doi: 10.1126/science.2144057.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division
  • Cell Line
  • Colonic Neoplasms
  • DNA Replication
  • Humans
  • Nuclear Proteins / genetics
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / physiology
  • Phosphoproteins / genetics*
  • Phosphoproteins / physiology
  • Plasmids
  • RNA, Messenger / genetics
  • Rectal Neoplasms
  • Transfection*
  • Tumor Cells, Cultured / cytology*
  • Tumor Suppressor Protein p53

Substances

  • Nuclear Proteins
  • Oncogene Proteins
  • Phosphoproteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53