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PMID: 12651607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays.

The American journal of pathology ·Vol. 162 ·No. 4 ·2003-04-00 ·Pages 1151-62

Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, Walter K, Sato N, Parker A, Ashfaq R, Jaffee E, Ryu B, Jones J, Eshleman JR, Yeo CJ, Cameron JL, Kern SE, Hruban RH, Brown PO, Goggins M

Abstract

Pancreatic cancer is the fifth leading cause of cancer death in the United States. We used cDNA microarrays to analyze global gene expression patterns in 14 pancreatic cancer cell lines, 17 resected infiltrating pancreatic cancer tissues, and 5 samples of normal pancreas to identify genes that are differentially expressed in pancreatic cancer. We found more than 400 cDNAs corresponding to genes that were differentially expressed in the pancreatic cancer tissues and cell lines as compared to normal pancreas. These genes that tended to be expressed at higher levels in pancreatic cancers were associated with a variety of processes, including cell-cell and cell-matrix interactions, cytoskeletal remodeling, proteolytic activity, and Ca(++) homeostasis. Two prominent clusters of genes were related to the high rates of cellular proliferation in pancreatic cancer cell lines and the host desmoplastic response in the resected pancreatic cancer tissues. Of 149 genes identified as more highly expressed in the pancreatic cancers compared with normal pancreas, 103 genes have not been previously reported in association with pancreatic cancer. The expression patterns of 14 of these highly expressed genes were validated by either immunohistochemistry or reverse transcriptase-polymerase chain reaction as being expressed in pancreatic cancer. The overexpression of one gene in particular, 14-3-3 sigma, was found to be associated with aberrant hypomethylation in the majority of pancreatic cancers analyzed. The genes and expressed sequence tags presented in this study provide clues to the pathobiology of pancreatic cancer and implicate a large number of potentially new molecular markers for the detection and treatment of pancreatic cancer.

MeSH Terms
Adenocarcinoma/genetics,pathology Biomarkers, Tumor/analysis DNA Methylation DNA, Complementary/genetics Gene Expression Regulation, Neoplastic Humans Multigene Family Neoplasm Invasiveness Oligonucleotide Array Sequence Analysis Pancreatic Neoplasms/genetics,pathology Polymerase Chain Reaction Tumor Cells, Cultured
Chemicals
Biomarkers, Tumor DNA, Complementary
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Iacobuzio-Donahue Christine A
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
Maitra Anirban
Olsen Mari
Lowe Anson W
van Heek N Tjarda
Rosty Christophe
Walter Kim
Sato Norihiro
Parker Antony
Ashfaq Raheela
Jaffee Elizabeth
Ryu Byungwoo
Jones Jessa
Eshleman James R
Yeo Charles J
Cameron John L
Kern Scott E
Hruban Ralph H
Brown Patrick O
Goggins Michael
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)63911-9
Published
2003-04-00
Pages
1151-62
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1851213
Subset
IM
Grants
NCI NIH HHS · P50 CA062924 · United States
NCI NIH HHS · U01 CA085129 · United States
NCI NIH HHS · CA62924 · United States
NCI NIH HHS · CA85129 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)63911-9 PMC Full Text View journal details
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