Suppression of human colorectal carcinoma cell growth by wild-type p53.
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.
Baker
S J
SJ
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231.
Markowitz
S
S
Fearon
E R
ER
Willson
J K
JK
Vogelstein
B
B
D002455:Cell Division; D002460:Cell Line; D003110:Colonic Neoplasms; D004261:DNA Replication; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics* / Q000502:physiology; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics; D012004:Rectal Neoplasms; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology*; D016159:Tumor Suppressor Protein p53
D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53