, Volume 42, Issue 10, pp 2054-2063

Presence of Two Signaling TGF-β Receptors in Human Pancreatic Cancer Correlates with Advanced Tumor Stage

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Abstract

Transforming growth factor-β (TGF-β)signal transduction is mediated via specific cellsurface signaling TGF-β receptors, most notably thetype I ALK5 (TβR-IALK5)and the type II(TβR-II). We evaluated TβR-IALK5 andTβR-II expression in 41 human pancreatic cancertissue samples and correlated these findings withclinical data of the patients. Northern blot analysisindicated that, in comparison with the normal pancreas,pancreatic adenocarcinomas exhibited 8.0-fold and4.5-fold increases (P < 0.01), respectively, in mRNAlevels encoding TβR-IALK5 andTβR-II. In situ hybridization showed that both TβR-IALK5 mRNAwere highly expressed in the majority of pancreaticcancer cells. Immunohistochemical analysis ofTβR-IALK5 and TβR-II revealedpositive immunostaining in 73% and 56% of the tumors, respectively. Both receptorswere concomitantly present in 54% of the pancreaticcancer samples. The presence ofTβR-IALK5 or TβR-II and theconcomitant presence of TβR-IALK5 and TβR-II in the cancer cells was associatedwith advanced tumor stage (P < 0.01). These findingsshow that in many human pancreatic cancers, increasedlevels of the two signaling TβRs are present. The presence of the signaling TβRs inadvanced tumor stages indicates a role in diseaseprogression.