Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-2-15
pubmed:abstractText
Prostate carcinogenesis is influenced by genetic alterations resulting in a biochemical condition that favors cell proliferation and survival. Studies of prostate carcinoma using comparative genomic hybridization and cDNA microarray analysis indicate that numerous biochemical processes may be affected during cellular transformation and progression to an invasive phenotype. Among the consistently observed tumor-associated changes are alterations in fatty acid metabolism that influence diverse cellular activities such as signaling, energy utilization, and membrane fluidity. Increases in fatty acid synthase (FAS) levels have been shown to be one of the earliest and most frequent molecular alterations in prostate carcinogenesis. We sought to identify tumor-associated changes in the expression of genes with functional roles associated with lipid metabolism. Defined populations of normal and neoplastic prostate epithelium were acquired by laser capture microdissection and transcript levels were measured by cDNA microarray hybridization. We determined that stearoyl-CoA desaturase (SCD) transcripts were downregulated in cancer relative to normal epithelium. These results were confirmed by quantitative PCR. Further analysis by immunohistochemical evaluation of radical prostatectomy samples employed a quantitative scoring system with a range of 0-300. The median SCD expression levels were 150, 45 and 10 for normal, PIN and carcinoma samples, respectively. Statistically significant differential SCD expression between normal and cancerous epithelium was determined at the p=0.001 level, and between PIN and prostate carcinoma at the p=0.03 level. Of these cases, 92% overexpressed fatty acid synthase (FAS) in cancerous cells and 84.7% exhibited the signature of FAS overexpression and SCD loss in prostate carcinoma as compared to normal prostate epithelium. These results indicate that loss of SCD expression is a frequent event in prostate adenocarcinoma, and further supports a role for altered lipid metabolism as a factor in the process of carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
563-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15609334-Blotting, Northern, pubmed-meshheading:15609334-Carcinoma, pubmed-meshheading:15609334-DNA, Complementary, pubmed-meshheading:15609334-Disease Progression, pubmed-meshheading:15609334-Down-Regulation, pubmed-meshheading:15609334-Fatty Acid Synthetase Complex, pubmed-meshheading:15609334-Fatty Acids, pubmed-meshheading:15609334-Humans, pubmed-meshheading:15609334-Immunohistochemistry, pubmed-meshheading:15609334-Lipid Metabolism, pubmed-meshheading:15609334-Male, pubmed-meshheading:15609334-Models, Biological, pubmed-meshheading:15609334-Nucleic Acid Hybridization, pubmed-meshheading:15609334-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15609334-Phenotype, pubmed-meshheading:15609334-Polymerase Chain Reaction, pubmed-meshheading:15609334-Prostatic Intraepithelial Neoplasia, pubmed-meshheading:15609334-Prostatic Neoplasms, pubmed-meshheading:15609334-RNA, pubmed-meshheading:15609334-RNA, Messenger, pubmed-meshheading:15609334-Stearoyl-CoA Desaturase, pubmed-meshheading:15609334-Tissue Distribution
pubmed:year
2005
pubmed:articleTitle
Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma.
pubmed:affiliation
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.