Publication Date:
1990-08-24
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, S J -- Markowitz, S -- Fearon, E R -- Willson, J K -- Vogelstein, B -- CA 43703/CA/NCI NIH HHS/ -- GM 07184/GM/NIGMS NIH HHS/ -- GM 07309/GM/NIGMS NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1990 Aug 24;249(4971):912-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2144057" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Division
;
Cell Line
;
Colonic Neoplasms
;
DNA Replication
;
Humans
;
Nuclear Proteins/genetics
;
Oncogene Proteins/*genetics/physiology
;
Phosphoproteins/*genetics/physiology
;
Plasmids
;
RNA, Messenger/genetics
;
Rectal Neoplasms
;
*Transfection
;
Tumor Cells, Cultured/*cytology
;
Tumor Suppressor Protein p53
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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