Differential localization of transforming growth factor-beta isoforms in 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 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.
Naef
M
M
Department of Medicine, University of California, Irvine 92697, USA.
Ishiwata
T
T
Friess
H
H
Büchler
M W
MW
Gold
L I
LI
Korc
M
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D003094:Collagen / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen