Background: Transforming growth factor βs (TGF-βs) constitute a family of bifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. Perturbations in TGF-β expression and function may lead to loss of negative constraints on cell growth. In this study, we examined TGF-β expression in human pancreatic cancer. Methods: The distribution of TGF-β isoforms in 60 human pancreatic cancers was examined using immunohistochemical, Northern blot, and in situ hybridization techniques. Results: Immunohistochemical analysis showed the presence of TGF-β1 (47% of tumors), TGF-β2 (42% of tumors), and TGF-β3 (40% of tumors) in the cancer cells. The presence of TGF-β2 was associated with advanced tumor stage (P < 0.05). Furthermore, there was a significant correlation between the absence of TGF-βs in the tumors and longer postoperative survival. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P < 0.001), 7- (P < 0.05), and 9-fold (P < 0.001) increases in the messenger RNA (mRNA) levels encoding TGF-β1, TGF-β2, and TGF-β3, respectively. By in situ hybridization, these mRNA moieties colocalized with their respective proteins in the cancer cells. Conclusions: These findings show that human pancreatic cancers show increased levels of TGF-β isoforms and enhanced TGF-β mRNA expression and suggest that the presence of TGF-βs in pancreatic cancer cells may contribute to disease progression.
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