IJCEP Copyright © 2007-All rights reserved.
Int J Clin Exp Pathol  1(6):510-517;2008.

Original Article
Differential Expression of Multiple Genes in Association with MADH4/DPC4/SMAD4
Inactivation in Pancreatic Cancer

Dengfeng Cao, Raheela Ashfaq, Michael G. Goggins, Ralph H. Hruban, Scott E. Kern and Christine A. Iacobuzio-Donahue

Departments of Pathology and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Hospital, Baltimore, MD
and Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX

Received 31 March, 2008; accepted and available online 10 April, 2008

Abstract: The Gene Logic Inc. Gene Express® tools and Affymetrix GeneChip® arrays were utilized to discover genes differentially expressed in
pancreatic cancers with MADH4/DPC4/SMAD4 gene inactivation. cDNA was prepared from thirteen pancreas cancer cell lines with known
MADH4 status (5 with wild-type MADH4 and 8 with inactivated MADH4) and hybridized to the complete Affymetrix Human Genome U133
GeneChip® set (arrays U133 A,B) for simultaneous analysis of 45,000 gene fragments corresponding to 33,000 known genes. 25 known
genes were identified as down-regulated at least three fold in the MADH4 mutant cancer cell lines. 9 were decreased in expression at least 5
fold, and 1 in particular (ID3) was decreased 23 fold. Only 2 of the 25 down-regulated genes (ID1 and ID3) have been previously reported as
MADH4-dependent targets, and the remaining 23 genes represent potential novel direct or indirect MADH4 downstream targets.
Immunolabeling for Id1 and Id3 did not show a relationship with known MADH4 status in pancreatic cancer tissues, suggesting additional
regulation of these two genes than activation by MadH4. Further investigations to validate and to determine the significance of these candidate
target genes in pancreatic carcinogenesis and progression are warranted.(IJCEP803016).

Key Words: DPC4, SMAD4, pancreas cancer, ID1, ID3, gene expression

Full text PDF

Address all correspondence to: Christine A. Iacobuzio-Donahue, M.D., Ph.D., The Johns Hopkins Hospital, Division of Gastrointestinal/Liver
Pathology, 1550 Orleans Street, CRB2 Rm 343, Baltimore, MD 21231. Tel: 410-955-3511; Fax: 410-614-0671; Email: