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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
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 correspondences 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: ciacobu@jhmi.edu
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 correspondences 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: ciacobu@jhmi.edu