Differential expression of transforming growth factor β receptors in human pancreatic adenocarcinoma

Background: Many cancer cells show resistance to transforming growth factor β (TGF-β)-mediated growth inhibition. This resistance to TGF-β is associated with an increased tumorigenic phenotype. Objective: In this study, we determined whether a loss in expression of TGF-β receptors or DPC4, an important down stream target of TGF-β signaling, might account for this lack of TGF-β sensitivity in pancreatic adenocarcinoma. Materials and Methods: To accomplish this, six established pancreatic cancer cell lines, twenty-six surgically resected tumor specimens of pancreatic adenocarcinoma and ten non-tumor pancreas tissues were analyzed for the mRNA expression of the three TGF-β receptors (RI, RII, and RIII) and DPC4. Results: We report here that five of six pancreatic cancer cell lines were not sensitive to TGF-β. All the ten non-tumor specimens of pancreas showed expression of RI, and DPC4; while nine of ten showed expression of RIII and eight of ten showed expression of RII. Five of six pancreatic cancer cell lines and 23 of 26 tumor specimens showed expression of RI. Two cell lines and about half (46%) of the tumor specimens did not express RII. Only two cell lines showed appreciable levels of RIII expression; while ten of 26 (38%) tumor specimens did not show expression of RIII. DPC4 expression was observed in three of the six (50%) cell lines and 19 of 24 (79%) tumor specimens. Conclusion: This study indicates that apart from the functional loss of DPC4 due to mutations or homozygous deletion, a lack of the TGF-β receptors, particularly RII and RIII, may contribute to a loss of TGF-β signaling in a population of pancreatic cancers.