title: Novel nuclear localization of fatty acid synthase correlates with prostate cancer aggressiveness.
abstract: Fatty acid synthase is up-regulated in a variety of cancers, including prostate cancer. Up-regulation of fatty acid synthase not only increases production of fatty acids in tumors but also contributes to the transformed phenotype by conferring growth and survival advantages. In addition, increased fatty acid synthase expression in prostate cancer correlates with poor prognosis, although the mechanism(s) by which this occurs are not completely understood. Because fatty acid synthase is expressed at low levels in normal cells, it is currently a major target for anticancer drug design. Fatty acid synthase is normally found in the cytosol; however, we have discovered that it also localizes to the nucleus in a subset of prostate cancer cells. Analysis of the fatty acid synthase protein sequence indicated the presence of a nuclear localization signal, and subcellular fractionation of LNCaP prostate cancer cells, as well as immunofluorescent confocal microscopy of patient prostate tumor tissue and LNCaPs confirmed nuclear localization of this protein. Finally, immunohistochemical analysis of prostate cancer tissue indicated that nuclear localization of fatty acid synthase correlates with Gleason grade, implicating a potentially novel role in prostate cancer progression. Possible clinical implications include improving the accuracy of prostate biopsies in the diagnosis of low- versus intermediate-risk prostate cancer and the uncovering of novel metabolic pathways for the therapeutic targeting of androgen-independent prostate cancer.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Madigan
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Rycyna
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Anil V
authors.initials: AV
authors.lastname: Parwani
authors.affiliation: Department of Biology, Tuskegee University, Tuskegee, Alabama.
authors.forename: Yeipyeng J
authors.initials: YJ
authors.lastname: Datiri
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Basudan
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Sobek
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cummings
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Per H
authors.initials: PH
authors.lastname: Basse
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Bacich
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Electronic address: okeeds@upmc.edu.
authors.forename: Denise S
authors.initials: DS
authors.lastname: O'Keefe
mesh_terms: D002467:Cell Nucleus / Q000201:enzymology*; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*
chemical_list: C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I