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Differential localization of transforming growth factor-beta isoforms in human gastric mucosa and overexpression in
1Department of Medicine, University of California, Irvine 92697, USA.
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.
Insights
Transforming growth factor beta (TGF-beta) isoforms play roles in gastric mucosa. Overexpression of all three TGF-beta isoforms in gastric cancer suggests involvement in disease development.
Area of Science:
- Gastroenterology
- Molecular Biology
- Oncology
Background:
- Transforming growth factor beta (TGF-beta) is a family of growth factors with diverse cellular functions.
- TGF-beta isoforms are known to regulate collagen production, a key component of the extracellular matrix.
Purpose of the Study:
- To investigate the expression and distribution of TGF-beta isoforms in normal human gastric mucosa and gastric carcinoma.
- To assess the correlation between TGF-beta expression and collagen type I alpha1 mRNA levels in gastric tissues.
Main Methods:
- Immunohistochemistry was used to determine the localization of TGF-beta isoforms in tissue samples.
- Northern blot analysis quantified mRNA levels of TGF-beta isoforms and collagen type I alpha1.
Main Results:
- TGF-beta1, TGF-beta2, and TGF-beta3 showed distinct localization patterns in normal gastric mucosa.
- Gastric cancers exhibited strong colocalization of all three TGF-beta isoforms within cancer cells.
- mRNA levels for TGF-beta1 and TGF-beta3 were significantly increased in gastric cancers compared to normal tissues.
- Collagen type I alpha1 mRNA levels were markedly elevated in gastric cancers.
Conclusions:
- TGF-beta isoforms are involved in the normal function of human gastric mucosa.
- Aberrant expression and colocalization of TGF-beta isoforms in gastric cancer cells may contribute to the pathobiology of the disease.
- Increased collagen type I alpha1 mRNA suggests a role for TGF-beta in matrix remodeling during gastric carcinogenesis.