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 (T beta R-I-ALK5) and the type II (T beta R-II). We evaluated T beta R-I-ALK5 and TPR-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 T beta R-I-ALK5 and T beta R-II. In situ hybridization showed that both T beta R-I-ALK5 and T beta R-II mRNA. were highly expressed in the majority of pancreatic cancer cells. Immunohistochemical analysis of T beta R-I-ALK5 and T beta R-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 T beta R-I-ALK5 or T beta R-II and the concomitant presence of T beta R-I-ALK5 and T beta R-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 T beta Rs are present. The presence of the signaling T beta Rs in advanced tumor stages indicates a role in disease progression.