D M Simeone1, T Pham, C D Logsdon. 1. Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. simeone@umich.edu
Abstract
OBJECTIVE: To investigate whether transforming growth factor beta (TGFbeta) signaling is disrupted in human pancreatic cancer cells, and to study the role of TGFbeta receptors and Smad genes. SUMMARY BACKGROUND DATA: TGFbeta is a known inhibitor of pancreatic growth. Disruption of the TGFbeta signaling pathway may play a role in pancreatic cancer development. METHODS: The effect of TGFbeta on the BxPC-3, MiaPaCa-2, and PANC-1 pancreatic cancer cell lines was evaluated by [3H]thymidine incorporation and a TGFbeta-responsive reporter assay. Expression of TGFbeta receptors and Smads 2 and 3 was assessed by cross-linking assays and reverse transcriptase-polymerase chain reaction (RT-PCR). The ability to restore TGFbeta responsiveness was evaluated by transfection of TGFbeta signaling components. RESULTS: TGFbeta produced little inhibition of DNA synthesis and did not activate a TGFbeta-responsive reporter in pancreatic cancer cell lines. 125TGFbeta cross-linking and RT-PCR confirmed the presence of TGFbeta receptors and Smad2 and Smad3 transcripts. Transfection of TGFbeta receptors or Smads 2 and 3 did not restore responsiveness. However, transfection of Smad4 into the BxPC-3 pancreatic cancer cell line restored TGFbeta responsiveness. CONCLUSIONS: Pancreatic cancer cells show loss of TGFbeta responsiveness. Smads 2 and 3 and TGFbeta receptors are not defective in the cell lines studied. Transfection of Smad4 into one of the cell lines restored TGFbeta responsiveness, suggesting an important role for Smad4 in pancreatic cancer. It is likely that other, as yet unidentified genes are important in TGFbeta resistance in pancreatic cancer cells.
OBJECTIVE: To investigate whether transforming growth factor beta (TGFbeta) signaling is disrupted in humanpancreatic cancer cells, and to study the role of TGFbeta receptors and Smad genes. SUMMARY BACKGROUND DATA: TGFbeta is a known inhibitor of pancreatic growth. Disruption of the TGFbeta signaling pathway may play a role in pancreatic cancer development. METHODS: The effect of TGFbeta on the BxPC-3, MiaPaCa-2, and PANC-1 pancreatic cancer cell lines was evaluated by [3H]thymidine incorporation and a TGFbeta-responsive reporter assay. Expression of TGFbeta receptors and Smads 2 and 3 was assessed by cross-linking assays and reverse transcriptase-polymerase chain reaction (RT-PCR). The ability to restore TGFbeta responsiveness was evaluated by transfection of TGFbeta signaling components. RESULTS:TGFbeta produced little inhibition of DNA synthesis and did not activate a TGFbeta-responsive reporter in pancreatic cancer cell lines. 125TGFbeta cross-linking and RT-PCR confirmed the presence of TGFbeta receptors and Smad2 and Smad3 transcripts. Transfection of TGFbeta receptors or Smads 2 and 3 did not restore responsiveness. However, transfection of Smad4 into the BxPC-3 pancreatic cancer cell line restored TGFbeta responsiveness. CONCLUSIONS:Pancreatic cancer cells show loss of TGFbeta responsiveness. Smads 2 and 3 and TGFbeta receptors are not defective in the cell lines studied. Transfection of Smad4 into one of the cell lines restored TGFbeta responsiveness, suggesting an important role for Smad4 in pancreatic cancer. It is likely that other, as yet unidentified genes are important in TGFbeta resistance in pancreatic cancer cells.
Authors: Rachel A Hesler; Jennifer J Huang; Mark D Starr; Victoria M Treboschi; Alyssa G Bernanke; Andrew B Nixon; Shannon J McCall; Rebekah R White; Gerard C Blobe Journal: Carcinogenesis Date: 2016-11-01 Impact factor: 4.944
Authors: Stephen J Murphy; Steven N Hart; Joema Felipe Lima; Benjamin R Kipp; Mitchell Klebig; Jennifer L Winters; Csilla Szabo; Lizhi Zhang; Bruce W Eckloff; Gloria M Petersen; Steven E Scherer; Richard A Gibbs; Robert R McWilliams; George Vasmatzis; Fergus J Couch Journal: Gastroenterology Date: 2013-08-02 Impact factor: 22.682
Authors: Thomas M Williams; Melissa E Williams; Joanne H Heaton; Thomas D Gelehrter; Jeffrey W Innis Journal: Nucleic Acids Res Date: 2005-08-08 Impact factor: 16.971
Authors: Stephanie H Greco; Lena Tomkötter; Anne-Kristin Vahle; Rae Rokosh; Antonina Avanzi; Syed Kashif Mahmood; Michael Deutsch; Sara Alothman; Dalia Alqunaibit; Atsuo Ochi; Constantinos Zambirinis; Tasnima Mohaimin; Mauricio Rendon; Elliot Levie; Mridul Pansari; Alejandro Torres-Hernandez; Donnele Daley; Rocky Barilla; H Leon Pachter; Daniel Tippens; Hassan Malik; Allal Boutajangout; Thomas Wisniewski; George Miller Journal: PLoS One Date: 2015-07-14 Impact factor: 3.240