title: Fatty acid synthase expression defines distinct molecular signatures in prostate cancer.
abstract: The androgen-regulated enzyme fatty acid synthase (FAS), required for de novo lipogenesis, is overexpressed in several cancers including prostate carcinoma and has been associated with aggressive disease. FAS expression was assessed in 81 prostate carcinomas, both by immunohistochemistry in tissue microarrays and by Affymetrix Hu95Av2 oligonucleotide arrays. Both FAS mRNA and protein were significantly overexpressed in prostate carcinomas compared with the corresponding normal tissue. FAS mRNA and protein expression increased substantially from normal to prostatic intraepithelial neoplasia, to low grade, to high grade, and to androgen-independent bone metastases. A significant correlation between FAS mRNA and protein expression was found in two thirds of the cases. In 17% of the cases, FAS protein levels were high despite low mRNA levels, and these tumors exhibited a distinct molecular signature when compared with tumors that did not express FAS protein. Whereas the latter group of tumors expressed some proapoptotic genes, tumors with high FAS levels overexpressed, among other genes, its transcriptional regulator, steroid regulator binding protein, and apolipoprotein E. These data demonstrate (1) the consistent overexpression of FAS in prostate carcinoma compared with the adjacent normal tissue, (2) a strong association between FAS and prostate tumor initiation and progression, (3) the highest FAS expression occurring in androgen-independent bone metastases, (4) the transcriptional and posttranscriptional regulation of FAS in the majority and in a subset of prostate cancers, respectively, and (5) most importantly, the identification by FAS expression of prostate tumors with unique molecular signatures and potentially diverse biologic behavior.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.forename: Edgard
authors.initials: E
authors.lastname: Graner
authors.forename: Phillip
authors.initials: P
authors.lastname: Febbo
authors.forename: Lisa
authors.initials: L
authors.lastname: Weinstein
authors.forename: Nandita
authors.initials: N
authors.lastname: Bhattacharya
authors.forename: Tamas
authors.initials: T
authors.lastname: Onody
authors.forename: Glenn
authors.initials: G
authors.lastname: Bubley
authors.forename: Stephen
authors.initials: S
authors.lastname: Balk
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
mesh_terms: D000728:Androgens / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D064429:Fatty Acid Synthases / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011467:Prostate / Q000201:enzymology*; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D064429:Fatty Acid Synthases