EXPRESSION OF GROWTH-FACTOR RECEPTOR-ENCODED MESSENGER-RNA BY COLONICEPITHELIAL-CELLS IS ALTERED IN INFLAMMATORY BOWEL-DISEASE

A link between inflammation of the colon in inflammatory bowel disease (IBD) and the increased risk of colon cancer in ulcerative colitis (U C) may be provided by growth factor receptor genes. Their expression m ay be altered in response to growth factors present in the mucosa, and this, in turn, may induce further genetic changes, linked to carcinog enesis, in the cells of the colonic epithelium. To test this hypothesi s, we assayed steady-state levels of eight growth factor receptor mRNA s in colonic epithelial cells of IBD patients and controls. Four of th ese genes (EGF-R, IGFI-R, CSF1-R, and PDGF-R-beta) were expressed in e pithelial cells, whereas four (erbB-2 erbB-3, NGF-R, and met) were not . The level of the former in involved or uninvolved IBD was considerab ly lower than in normal epithelial cells from either sporadic colon ca ncer or diverticulitis patients. In contrast, expression was much high er in IBD patients with colon tumors than in active chronic IBD. The l evel of PDGF-R-beta mRNA was two- to fourfold higher in involved than in uninvolved areas of the colons of two UC patients, but not in one C rohn's disease patient. Message abundance of its ligand, PDGF-beta, ho wever, was the same in paired UC samples. The pattern of expression of PDGF-beta and cripto was identical to that of EGF-R, whereas the leve l of mRNA of amphiregulin was the same in active chronic IBD and IBD p atients with tumors. A fourth growth factor, Kfgf, was not expressed. Increased levels of PDGF-R-beta mRNA in involved UC relative to uninvo lved UC may be related to the disease process in UC. Decreased express ion of growth factor- and growth factor receptor-encoded mRNA in activ e chronic IBD may be related to the disease process, or it may be an e ffect of steroid therapy undergone by these patients. Enhanced express ion of these genes in IBD patients with tumors compared to those witho ut tumors suggests that this may be a marker for development of colon cancer in IBD.