Presence of two signaling TGF-beta receptors in human pancreatic cancer correlates with advanced tumor stage.

Transforming growth factor-beta (TGF-beta) signal transduction is mediated via specific cell surface signaling TGF-beta receptors, most notably the type I ALK5 (TbetaR-I[ALK5]) and the type II (TbetaR-II). We evaluated TbetaR-I(ALK5) and TbetaR-II expression in 41 human pancreatic cancer tissue samples and correlated these findings with clinical data of the patients. Northern blot analysis indicated that, in comparison with the normal pancreas, pancreatic adenocarcinomas exhibited 8.0-fold and 4.5-fold increases (P < 0.01), respectively, in mRNA levels encoding TbetaR-I(ALK5) and TbetaR-II. In situ hybridization showed that both TbetaR-I(ALK5) and TbetaR-II mRNA were highly expressed in the majority of pancreatic cancer cells. Immunohistochemical analysis of TbetaR-I(ALK5) and TbetaR-II revealed positive immunostaining in 73% and 56% of the tumors, respectively. Both receptors were concomitantly present in 54% of the pancreatic cancer samples. The presence of TbetaR-I(ALK5) or TbetaR-II and the concomitant presence of TbetaR-I(ALK5) and TbetaR-II in the cancer cells was associated with advanced tumor stage (P < 0.01). These findings show that in many human pancreatic cancers, increased levels of the two signaling TbetaRs are present. The presence of the signaling TbetaRs in advanced tumor stages indicates a role in disease progression.