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.


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 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.


CONCLUSIONS
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.
Rochlitz
C F
CF
Department Innere Medizin, Abteilung für Onkologie, Kantonsspital Basel, Switzerland.
Heide
I
I
Thiede
C
C
Herrmann
R
R
de Kant
E
E
D015179:Colorectal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger