Linked Life Data

15753353

Source:http://linkedlifedata.com/resource/pubmed/id/15753353

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-3-8
pubmed:abstractText
Invasive pancreatic cancer is thought to develop through a series of noninvasive duct lesions known as pancreatic intraepithelial neoplasia (PanIN). We used cDNA microarrays interrogating 15,000 transcripts to identify 49 genes that were differentially expressed in microdissected early PanIN lesions (PanIN-1B/2) compared with microdissected normal duct epithelium. In this analysis, a cluster of extrapancreatic foregut markers, including pepsinogen C, MUC6, KLF4, and TFF1, was found to be up-regulated in PanIN. Up-regulation of these genes was further validated using combinations of real-time reverse transcription-PCR, in situ hybridization, and immunohistochemistry in a total of 150 early PanIN lesions from 81 patients. Identification of these gastrointestinal transcripts in human PanIN prompted assessment of other foregut markers by both semiquantitative and real-time reverse transcription-PCR, revealing similar up-regulation of Sox-2, Gastrin, HoxA5, GATA4/5/6, Villin and Forkhead 6 (Foxl1). In contrast to frequent expression of multiple gastric epithelial markers, the intestinal markers intestinal fatty acid binding protein, CDX1 and CDX2 were rarely expressed either in PanIN lesions or in invasive pancreatic cancer. Hedgehog pathway activation induced by transfection of immortalized human pancreatic ductal epithelial cells with Gli1 resulted in up-regulation of the majority of foregut markers seen in early PanIN lesions. These data show frequent up-regulation of foregut markers in early PanIN lesions and suggest that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1619-26
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15753353-Carcinoma, Pancreatic Ductal, pubmed-meshheading:15753353-Carcinoma in Situ, pubmed-meshheading:15753353-DNA-Binding Proteins, pubmed-meshheading:15753353-Epithelial Cells, pubmed-meshheading:15753353-Gene Expression Profiling, pubmed-meshheading:15753353-Hedgehog Proteins, pubmed-meshheading:15753353-Humans, pubmed-meshheading:15753353-In Situ Hybridization, pubmed-meshheading:15753353-Kruppel-Like Transcription Factors, pubmed-meshheading:15753353-Mucin-6, pubmed-meshheading:15753353-Mucins, pubmed-meshheading:15753353-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15753353-Pancreatic Ducts, pubmed-meshheading:15753353-Pancreatic Neoplasms, pubmed-meshheading:15753353-Pepsinogen C, pubmed-meshheading:15753353-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:15753353-Signal Transduction, pubmed-meshheading:15753353-Trans-Activators, pubmed-meshheading:15753353-Transcription Factors, pubmed-meshheading:15753353-Tumor Markers, Biological, pubmed-meshheading:15753353-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells.
pubmed:affiliation
Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't