Expression of protooncogene-encoded mRNA by colonic epithelial cells in inflammatory bowel disease

Abstract

Protooncogenes are cell cycle-related genes that are involved in cell growth of proliferation. Alterations in the level of expression of these genes, or expression of aberrant gene productions, have been observed in tumors and precancerous conditions. To determine if expression of these genes is altered in patients with inflammatory bowel disease (IBD) --who are at risk for development of colon cancer--we assayed transcripts of 15 protooncogenes in colonic epithelial cells of IBD patients and controls. Nine of these genes (H-ras, c-myc, c-fos, c-jun, junB, N-myc, 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 transcripts of H-ras and five nuclear protooncogenes (c-myc, c-fos, c-jun, junB, and N-myc) were lower in epithelial cells from involved or uninvolved IBD samples than in normal epithelial cells from either sporadic colon cancer or diverticulitis patients. The level of c-fos mRNA was two- to threefold higher in involved than in uninvolved areas of the colons of two ulcerative colitis (UC) patients, but not in one Crohn's disease (CD) patient. Message abundance of c-abl transcripts was two- 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 considerably higher in IBD patients resected for colon cancer than in patients 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 transcript in UC may be a diagnostic marker for UC and may be related to the rate of cell turnover in these diseases. Enhanced expression of c-yes in IBD patients with tumors compared to active chronic IBD and controls suggests that expression of this gene may be a marker for development of colon cancer in IBD.