PRESENCE OF 2 SIGNALING TGF-BETA RECEPTORS IN HUMAN PANCREATIC-CANCERCORRELATES WITH ADVANCED TUMOR STAGE

Transforming growth factor-beta (TGF-beta) signal transduction is medi ated via specific cell surface signaling TGF-beta receptors, most nota bly the type I ALK5 (T beta R-I-ALK5) and the type II (T beta R-II). W e evaluated T beta R-I-ALK5 and TPR-II expression in 41 human pancreat ic cancer tissue samples and correlated these findings with clinical d ata of the patients. Northern blot analysis indicated that, in compari son 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 analy sis of T beta R-I-ALK5 and T beta R-II revealed positive immunostainin g in 73% and 56% of the tumors, respectively. Both receptors were conc omitantly present in 54% of the pancreatic cancer samples. The presenc e 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 huma n 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.