Expression of putative anticancer targets in familial adenomatous polyposis and its association with the APC mutation status.
Several substances interfering with colorectal carcinogenesis may reduce or prevent adenoma formation in familial adenomatous polyposis (FAP), an inherited predisposition to colorectal cancer. This study determined the expression of genes coding for putative anticancer targets (COX-2, iNOS, MMP-7, ODC, PKCbeta, PPARgamma, RXRalpha, RXRbeta, RXRgamma) in FAP patients to provide one of the rationales for the design of chemotherapy and -prevention strategies. Gene expression was assessed by TaqMan analysis in colonic tissue of 9 FAP patients with mutations in the APC gene (APCpos), 5 FAP patients without identified genetic defect (APCneg), and 3 healthy individuals. Among the examined genes, PKCbeta and MMP-7 were most consistently altered in adenoma tissue relative to matched mucosa. Intriguingly, ODC was clearly overexpressed in polyps from APCpos but not APCneg patients. Furthermore, PKCbeta, MMP-7, ODC, and COX-2 as well as all RXRs displayed altered expression in apparently healthy FAP mucosa as opposed to that of healthy individuals. Our data suggests PKCbeta and MMP-7 to be the most suited as anticancer targets among the genes studied.
Humar
B
B
Division of Medical Genetics, DKBW, Research Group Human Genetics, University Hospital, Basel, Switzerland.
D'Orazio
D
D
Albrecht
C
C
Bauerfeind
P
P
Muller
H
H
Dobbie
Z
Z
Bendik
I
I
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D015870:Gene Expression; D017491:Genes, APC; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D016588:Anticarcinogenic Agents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger