Evidence for a mutual regulation of p53 and c-myc expression in human colorectal cancer metastases

Background : Alterations of the c-myc and the p53 genes occur in a majority of human colorectal cancers, and functional interaction between these two genes has recently been suggested. Patients and methods : We analyzed p53 sequence and c-myc and p53 mRNA expression in 26 metastases and 4 advanced primaries of human colorectal cancer. Results : Twenty-one of the 30 tumors (=70%) carried mutations of the p53 gene. In these samples, c-myc and p53 were overexpressed in 70% (15/21) and 71% (14/20) of evaluable cases, respectively, while in tumors carrying only wild-type p53, overexpression of c-myc and p53 was observed in only 33% (3/9 ; p < 0.05) and 22% (2/9 ; p < 0.01), respectively. Expression of p53 and c-myc were positively correlated (p = 0.014 ; r = 0.563) in tumors carrying a p53 mutation, but not in those with only wild-type p53. Conclusion : We conclude that c-myc might induce p53 expression in human colorectal cancer and that wild-type but not mutant p53 might be involved in a negative feedback regulation of c-myc expression. The abrogation of this normal control mechanism seems to be an essential step during colorectal tumorigenesis and metastatic progression.