title: Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays.
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.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Mari
authors.initials: M
authors.lastname: Olsen
authors.forename: Anson W
authors.initials: AW
authors.lastname: Lowe
authors.forename: N Tjarda
authors.initials: NT
authors.lastname: van Heek
authors.forename: Christophe
authors.initials: C
authors.lastname: Rosty
authors.forename: Kim
authors.initials: K
authors.lastname: Walter
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Antony
authors.initials: A
authors.lastname: Parker
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jaffee
authors.forename: Byungwoo
authors.initials: B
authors.lastname: Ryu
authors.forename: Jessa
authors.initials: J
authors.lastname: Jones
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kern
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D019175:DNA Methylation; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D005810:Multigene Family; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018076:DNA, Complementary