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.