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

Int J Cancer. 1997 Apr 10;71(2):131-7. doi: 10.1002/(sici)1097-0215(19970410)71:2<131::aid-ijc1>3.0.co;2-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Blotting, Northern
  • Collagen / metabolism
  • Female
  • Gastric Mucosa / metabolism*
  • Gastric Mucosa / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Transforming Growth Factor beta / metabolism*

Substances

  • RNA, Messenger
  • Transforming Growth Factor beta
  • Collagen