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

Markus Naef, Toshiyuki Ishiwata, Helmut Friess, Markus W. Büchler, Leslie I. Gold, Murray Korc

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Transforming growth factor β (TGF-β) isoforms comprise a family of multifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. We examined TGF-β expression in normal human gastric mucosa and carcinoma. The distribution and expression of TGF-β 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-βs regulate collagen expression, collagen type I α1 mRNA amounts were also examined. Immunohistochemical analysis of normal human gastric tissue samples indicated that TGF-β1 localized principally in parietal cells but also in some surface mucus cells, TGF-β2 was present exclusively in chief cells and TGF- β3 was present in parietal, chief and mucus cells. In the gastric cancers, strong colocalization of TGF-β1, -β2 and -β3 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-β1 and TGF-β3, respectively. In contrast, TGF-β2 mRNA amounts were comparable in both groups. Northern blot analysis showed a 10- fold increase in human collagen type I α1 mRNA amounts compared to normal gastric tissue. These findings imply a role for TGF-βs in normal human gastric mucosa function, and raise the possibility that the aberrant colocalization and overexpression of all 3 TGF-β isoforms in human gastric cancer cells in vivo may contribute to the pathobiology of gastric carcinoma.

Original languageEnglish (US)
Pages (from-to)131-137
Number of pages7
JournalInternational Journal of Cancer
Volume71
Issue number2
DOIs
StatePublished - Jun 27 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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