High-throughput drug screening of the DPC4 tumor-suppressor pathway in human pancreatic cancer cells

Annals of Surgery
T A SohnS E Kern

Abstract

To screen a library of small chemicals for compounds that activate the DPC4 signal transduction pathway in a human pancreatic cancer cell line. Various tumor-suppressor genes are mutated in all human cancers. Specifically, DPC4 (deleted in pancreatic carcinoma, locus 4 or MADH4/SMAD4) is a tumor-suppressor gene mutated in approximately 50% of human pancreatic adenocarcinomas. DPC4 plays an important role in the well-studied transforming growth factor-beta (TGFbeta) signaling pathway. It would be useful to identify therapies that augment or restore the downstream functions of this critical signal transduction pathway, in hopes that such therapy would have a rational role in anticancer therapy. Using a commercially available plasmid vector with a luciferase reporter gene already incorporated, a DPC4-specific reporter construct was genetically engineered. This was done by inserting six copies of the palindromic Smad binding element (6SBE), which is a DNA binding element specific for DPC4, in front of the minimal promoter in the plasmid. This construct was then stably integrated into the genome of a human pancreatic cancer cell line (PANC-1) that has wild-type DPC4. Several stably transfected clones were tested for basal luciferase...Continue Reading

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Citations

Oct 3, 2003·Biochemical and Biophysical Research Communications·Keith B GlaserSteven K Davidsen
Jan 16, 2002·Current Opinion in Genetics & Development·Lalage M Wakefield, Anita B Roberts
Jun 11, 2002·Methods : a Companion to Methods in Enzymology·G Wynne AhernePaul Workman
Mar 26, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Xiaoqiu Wu, Udo Oppermann
Feb 16, 2005·Anti-cancer Drugs·Valeria Gonzalez-Nicolini, Martin Fussenegger
Jul 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yunfeng CuiJames R Eshleman
May 5, 2010·World Journal of Gastroenterology : WJG·Suntaek HongKi-Baik Hahm
Nov 28, 2012·Investigational New Drugs·Robert T DorrDaniel D Von Hoff
May 15, 2007·Biochemical Pharmacology·Keith B Glaser
Dec 4, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xiang XiaZhengjun Qiu
Feb 24, 2015·Magnetic Resonance Imaging·Rossana RitelliPasquina Marzola
Dec 14, 2016·BioMed Research International·Hang YinHailin Liu

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