Differential localization of transforming growth factor-β isoforms in human gastric mucosa and overexpression in gastric carcinoma

✍ Scribed by Markus Naef; Toshiyuki Ishiwata; Helmut Friess; Markus W. Büchler; Leslie I. Gold; Murray Korc

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 435 KB
• Volume: 71
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970410)71:2<131::aid-ijc1>3.0.co;2-1

✦ Synopsis

Transforming growth factor beta (TGF-beta) isoforms comprise a family of multifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. We examined TGF-beta expression in normal human gastric mucosa and carcinoma. The distribution and expression of TGF-beta isoforms in 4 normal mucosa samples from organ donors, in 12 normal mucosa samples adjacent to gastric cancer and in 12 gastric carcinomas were examined using immunohistochemistry and Northern blot analysis. Because TGF-beta s regulate collagen expression, collagen type I alpha1 mRNA amounts were also examined. Immunohistochemical analysis of normal human gastric tissue samples indicated that TGF-beta1 localized principally in parietal cells but also in some surface mucus cells, TGF-beta2 was present exclusively in chief cells and TGF-beta3 was present in parietal, chief and mucus cells. In the gastric cancers, strong colocalization of TGF-beta1, -beta2 and -beta3 was 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-beta1 and TGF-beta3, respectively. In contrast, TGF-beta2 mRNA amounts were comparable in both groups. Northern blot analysis showed a 10-fold increase in human collagen type I alpha1 mRNA amounts compared to normal gastric tissue. These findings imply a role forTGF-beta s in normal human gastric mucosa function, and raise the possibility that the aberrant colocalization and overexpression of all 3 TGF-beta isoforms in human gastric cancer cells in vivo may contribute to the pathobiology of gastric carcinoma.