TY - JOUR
T1 - Differential localization of transforming growth factor-β isoforms in human gastric mucosa and overexpression in gastric carcinoma
AU - Naef, Markus
AU - Ishiwata, Toshiyuki
AU - Friess, Helmut
AU - Büchler, Markus W.
AU - Gold, Leslie I.
AU - Korc, Murray
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031005355&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19970410)71:2<131::AID-IJC1>3.0.CO;2-1
DO - 10.1002/(SICI)1097-0215(19970410)71:2<131::AID-IJC1>3.0.CO;2-1
M3 - Article
C2 - 9139831
AN - SCOPUS:0031005355
SN - 0020-7136
VL - 71
SP - 131
EP - 137
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -
