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

Transforming growth factor-β (TGF-β) signal transduction is mediated via specific cell surface signaling TGF-β receptors, most notably the type I ALK5 (TβR-I(ALK5)) and the type II (TβR-II). We evaluated TβR-(ALK5) and TβR-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 TβR-I(ALK5) and TβR-II. In situ hybridization showed that both TβR-I(ALK5) and TβR-II mRNA were highly expressed in the majority of pancreatic cancer cells. Immunohistochemical analysis of TβR-I(ALK5) and TβR-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 TβR- I(ALK5) or TβR-II and the concomitant presence of TβR-I(ALK5) and TβR-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 TβRs are present. The presence of the signaling TβRs in advanced tumor stages indicates a role in disease progression.