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Differential localization of transforming growth factor-β isoforms in human gastric mucosa and overexpression in gastric carcinoma
Authors:Markus Naef  Toshiyuki Ishiwata  Helmut Friess  Markus W Büchler  Leslie I Gold  Murray Korc
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 1 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 1 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 bcontribute to the pathobiology of gastric carcinoma. Int. J. Cancer 71:131–137, 1997. © 1997 Wiley-Liss, Inc.
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