DIFFERENTIAL LOCALIZATION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMSIN HUMAN GASTRIC-MUCOSA AND OVEREXPRESSION IN GASTRIC-CARCINOMA

Transforming growth factor beta (TGF-beta) isoforms comprise a family of multifunctional polypeptide growth factors that either inhibit or s timulate cell proliferation. We examined TGF-beta expression in normal human gastric mucosa and carcinoma. The distribution and expression o f TGF-beta isoforms in 4 normal mucosa samples from organ donors, in 1 2 normal mucosa samples adjacent to gastric cancer and in 12 gastric c arcinomas were examined using immunohistochemistry and Northern blot a nalysis. Because TGF-beta s regulate collagen expression, collagen typ e I alpha(1) mRNA amounts were also examined. Immunohistochemical anal ysis of normal human gastric tissue samples indicated that TGF-beta(1) localized principally in parietal cells but also in some surface mucu s cells, TGF-beta(3) was present exclusively in chief cells and TGF-be ta(3) was present in parietal, chief and mucus cells. In the gastric c ancers, strong colocalization of TGF-beta(1), -beta(2) and -beta(3) wa s evident in the cancer cells. Northern blot analysis indicated that, compared to normal gastric tissue, gastric cancers showed a 4.8- and 6 -fold increase in mRNA amounts encoding TGF-beta(1) and TGF-beta(3), r espectively. In contrast, TGF-beta(2) mRNA amounts were comparable in both groups. Northern blot analysis showed a 10-fold increase in human collagen type I alpha(1) mRNA amounts compared to normal gastric tiss ue. These findings imply a role for TGF-beta s in normal human gastric mucosa function, and raise the possibility that the aberrant colocali zation and overexpression of all 3 TGF-beta isoforms in human gastric cancer cells in vivo may contribute to the pathobiology of gastric car cinoma. (C) 1997 Wiley-Liss, Inc.