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 inhe rited predisposition to colorectal cancer. This study determined the expres sion of genes coding for putative anticancer targets (COX-2, iNOS, MMP-7, O DC, PKC beta, PPAR gamma, RXR alpha, RXR beta, RXR gamma) in FAP patients t o provide one of the rationales for the design of chemotherapy and -prevent ion strategies. Gene expression was assessed by TaqMan analysis in colonic tissue of 9 FAP patients with mutations in the APC gene (APC(pos)), 5 FAP p atients without identified genetic defect (APC(neg)), and 3 healthy individ uals. Among the examined genes, PKC beta and MMP-7 were most consistently a ltered in adenoma tissue relative to matched mucosa. Intriguingly, ODC was clearly overexpressed in polyps from APC(pos) but not APC(neg) patients. Fu rthermore, PKC beta, MMP-7, ODC, and COX-2 as well as all RXRs displayed al tered expression in apparently healthy FAP mucosa as opposed to that of hea lthy individuals. Our data suggests PKC beta and MMP-7 to be the most suite d as anticancer targets among the genes studied.