TYPE-II TGF-BETA RECEPTOR EXPRESSION IN INTESTINAL-CELL LINES AND IN THE INTESTINAL-TRACT

The recent identification and cloning of mammalian transforming growth factor beta (TGF beta) receptors permits further analysis of the impo rtance of the TGF beta family in intestinal biology, Expression of the type II TGF beta receptor was examined in gastrointestinal cell lines and tissues, The 5.5 kb type II mRNA species was detected in poly-(A) mRNA isolated from the rat small: bowel and colon, Northern blot anal ysis of RNA isolated from epithelial and non-epithelial small intestin al cell fractions showed the majority of receptor mRNA localized in th e non-epithelial compartment. Immunohistochemical localization in the small intestine and colon supported the RNA findings; that is, express ion was greatest in the lamina propria and muscularis. Staining was al so detectable in the epithelium, where it was mast prominent in the vi llus tip cells and absent in crypt cells, These findings mirror expres sion of TGF beta in the epithelial compartment. The IEC-6, IPEC and RI E-1 cell lines, all of which are non-transformed, were growth inhibite d by TGF beta and expressed type II receptor mRNA and protein, By cont rast, the ras-transfected RIE-1, HT-29, Caco-2 and SW-620 transformed lines were not growth inhibited by TGF beta and all demonstrated a mar ked reduction in type II TGF beta receptor mRNA expression and protein abundance by cross-linking, In conclusion, (i) colocalization of both ligand and receptor establishes the existence of potential autocrine and/or paracrine pathways for TGF beta in the normal intestine and (ii ) down-regulation of the type II TGF beta receptor occurs in associati on with cellular transformation and may contribute to intestinal carci nogenesis.