title: Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the pancreas.
abstract: The molecular pathology of precursor lesions leading to invasive pancreatic ductal adenocarcinomas remains relatively unknown. We have applied cDNA microarray analysis to characterize gene expression profiles in a series of intraductal papillary-mucinous tumors (IPMTs) of the pancreas, which represents one of the alternative routes of intraepithelial progression to full malignancy in the pancreatic duct system. Using a cDNA microarray containing 4992 human genes, we screened a total of 13 IPMTs including nine noninvasive and four invasive cases. Expression change in more than half of the tumors was observed for 120 genes, ie, 62 up-regulated and 58 down-regulated genes. Some of the up-regulated genes in this study have been previously described in classical pancreatic carcinomas such as lipocalin 2, galectin 3, claudin 4, and cathepsin E. The most highly up-regulated genes in IPMTs corresponded to three members of the trefoil factor family (TFF1, TFF2, and TFF3). Immunohistochemistry performed on five genes found to be differentially expressed at the RNA level (TFF1, TFF2, TFF3, lipocalin 2, and galectin 3) showed a good concordance between transcript level and protein abundance, except for TFF2. Hierarchical clustering organized the cases according to the dysplastic and invasive phenotype of theIPMTs. This analysis has permitted us to implicate several genes (caveolin 1, glypican 1, growth arrest-specific 6 protein, cysteine-rich angiogenic inducer 61) in tumor progression. The observation that several genes are differentially expressed both in IPMTs and pancreatic carcinomas suggests that they may be involved at an early stage of pancreatic carcinogenesis.
authors: Cancer Research UK Molecular Oncology Unit, Imperial College School of Medicine at Hammersmith Campus, London, United Kingdom.
authors: Benoit
authors: B
authors: Terris
authors: Ekaterina
authors: E
authors: Blaveri
authors: Tatjana
authors: T
authors: Crnogorac-Jurcevic
authors: Melanie
authors: M
authors: Jones
authors: Edoardo
authors: E
authors: Missiaglia
authors: Philippe
authors: P
authors: Ruszniewski
authors: Alain
authors: A
authors: Sauvanet
authors: Nicholas R
authors: NR
authors: Lemoine
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology*; D002461:Cell Line, Transformed; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000071164:Trefoil Factor-2
chemical_list: D012334:RNA, Neoplasm; C000604007:TFF2 protein, human; D000071164:Trefoil Factor-2