Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma

Stacy Moore, Beatrice Knudsen, Lawrence D. True, Sarah Hawley, Ruth Etzioni, Christian Wade, David Gifford, Ilsa Coleman, Peter S. Nelson

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Prostate carcinogenesis is influenced by genetic alterations result ing 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.

Original languageEnglish (US)
Pages (from-to)563-571
Number of pages9
JournalInternational Journal of Cancer
Volume114
Issue number4
DOIs
StatePublished - Apr 20 2005
Externally publishedYes

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Stearoyl-CoA Desaturase
Prostate
Carcinoma
Fatty Acid Synthases
Epithelium
Carcinogenesis
Oligonucleotide Array Sequence Analysis
Lipid Metabolism
Biochemical Phenomena
Laser Capture Microdissection
Neoplasms
Membrane Fluidity
Comparative Genomic Hybridization
Microarray Analysis
Prostatectomy
Cell Survival
Adenocarcinoma
Fatty Acids
Down-Regulation
Cell Proliferation

Keywords

  • Lipid metabolism
  • Microarray
  • Microdissection
  • Prostate cancer
  • Stearoyl-CoA desaturase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Moore, S., Knudsen, B., True, L. D., Hawley, S., Etzioni, R., Wade, C., ... Nelson, P. S. (2005). Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma. International Journal of Cancer, 114(4), 563-571. https://doi.org/10.1002/ijc.20773

Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma. / Moore, Stacy; Knudsen, Beatrice; True, Lawrence D.; Hawley, Sarah; Etzioni, Ruth; Wade, Christian; Gifford, David; Coleman, Ilsa; Nelson, Peter S.

In: International Journal of Cancer, Vol. 114, No. 4, 20.04.2005, p. 563-571.

Research output: Contribution to journalArticle

Moore, S, Knudsen, B, True, LD, Hawley, S, Etzioni, R, Wade, C, Gifford, D, Coleman, I & Nelson, PS 2005, 'Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma', International Journal of Cancer, vol. 114, no. 4, pp. 563-571. https://doi.org/10.1002/ijc.20773
Moore, Stacy ; Knudsen, Beatrice ; True, Lawrence D. ; Hawley, Sarah ; Etzioni, Ruth ; Wade, Christian ; Gifford, David ; Coleman, Ilsa ; Nelson, Peter S. / Loss of stearoyl-CoA desaturase expression is a frequent event in prostate carcinoma. In: International Journal of Cancer. 2005 ; Vol. 114, No. 4. pp. 563-571.
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