EXPRESSION OF PROTOONCOGENE-ENCODED MESSENGER-RNA BY COLONIC EPITHELIAL-CELLS IN INFLAMMATORY BOWEL-DISEASE

Protooncogenes are cell cycle-related genes that are involved in cell growth or proliferation, Alterations in the level of expression of the se genes, or expression of aberrant gene products, have been observed in tumors and precancerous conditions. To determine if expression of t hese genes is altered in patients with inflammatory bowel disease (IBD )-who are at risk for development of colon cancer-we assayed transcrip ts of 15 protooncogenes in colonic epithelial cells of IBD patients an d controls, Nine of these genes (H-ms, c-myc, c-fos, c-jun, junB, N-my c, c-abl, c-yes, and p53) were expressed in epithelial cells, whereas two (RB1 and N-ras) were not. Expression of four other genes (c-src, K -ras, c-raf; and c-myb) was observed, but the intensity of these bands was too low for densitometric analysis, The steady-state levels of tr anscripts of H-ras and five nuclear protooncogenes (c-myc, c-fos, c-ju n, junB, and N-myc) were lower in epithelial cells from involved or un involved IBD samples than in normal epithelial cells from either spora dic colon cancer or diverticulitis patients, The level of c-fos mRNA w as two- to threefold higher in involved than in uninvolved areas of th e colons of two ulcerative colitis (UC) patients, but not in one Crohn 's disease (CD) patient. Message abundance of c-abl transcripts was tw o- to threefold lower in UC epithelial cells than in either the CD or control samples, The steady-state level of c-yes-encoded mRNA was cons iderably higher in IBD patients resected for colon cancer than in pati ents resected for active chronic IBD or in controls. The level of p53 message was constant in these samples. Increased levels of c-fos mRNA in involved UC relative to uninvolved UC may be related to the disease process. Decreased expression of c-abl transcripts in UC may be a dia gnostic marker for UC and may be related to the rate of cell turnover in these diseases. Enhanced expression of eyes in IBD patients with tu mors compared to active chronic IBD and controls suggests that express ion of this gene may be a marker for development of colon cancer in IB D.