title: Differential expression of transforming growth factor beta receptors in human pancreatic adenocarcinoma.
abstract: BACKGROUND
  Many cancer cells show resistance to transforming growth factor beta (TGF-beta)-mediated growth inhibition. This resistance to TGF-beta is associated with an increased tumorigenic phenotype.
  
  
  OBJECTIVE
  In this study, we determined whether a loss in expression of TGF-beta receptors or DPC4, an important down stream target of TGF-beta signaling, might account for this lack of TGF-beta sensitivity in pancreatic adenocarcinoma.
  
  
  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-beta receptors (RI, RII, and RIII) and DPC4.
  
  
  RESULTS
  We report here that five of six pancreatic cancer cell lines were not sensitive to TGF-beta. 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.
  
  
  CONCLUSIONS
  This study indicates that apart from the functional loss of DPC4 due to mutations or homozygous deletion, a lack of the TGF-beta receptors, particularly RII and RIII, may contribute to a loss of TGF-beta signaling in a population of pancreatic cancers.
authors.affiliation: Department of Surgery, University of Texas Health Science Center, San Antonio 78284, USA.
authors.forename: K
authors.initials: K
authors.lastname: Venkatasubbarao
authors.forename: M M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: M
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: C
authors.initials: C
authors.lastname: Swiderski
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.forename: W R
authors.initials: WR
authors.lastname: Gower
authors.forename: K F
authors.initials: KF
authors.lastname: Salhab
authors.forename: P
authors.initials: P
authors.lastname: McGrath
authors.forename: W
authors.initials: W
authors.lastname: Strodel
authors.forename: J W
authors.initials: JW
authors.lastname: Freeman
mesh_terms: D030201:Activin Receptors, Type I; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D011509:Proteoglycans / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C071736:betaglycan; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II