title: Characterisation of the androgen regulation of glycine N-methyltransferase in prostate cancer cells.
abstract: The development and growth of prostate cancer is dependent on androgens; thus, the identification of androgen-regulated genes in prostate cancer cells is vital for defining the mechanisms of prostate cancer development and progression and developing new markers and targets for prostate cancer treatment. Glycine N-methyltransferase (GNMT) is a S-adenosylmethionine-dependent methyltransferase that has been recently identified as a novel androgen-regulated gene in prostate cancer cells. Although the importance of this protein in prostate cancer progression has been extensively addressed, little is known about the mechanism of its androgen regulation. Here, we show that GNMT expression is stimulated by androgen in androgen receptor (AR) expressing cells and that the stimulation occurs at the mRNA and protein levels. We have identified an androgen response element within the first exon of the GNMT gene and demonstrated that AR binds to this element in vitro and in vivo. Together, these studies identify GNMT as a direct transcriptional target of the AR. As this is an evolutionarily conserved regulatory element, this highlights androgen regulation as an important feature of GNMT regulation.
authors.affiliation: Department of Surgery and Cancer, Imperial College London, Imperial Centre for Translational and Experimental Medicine, London W12 0NN, UK School of Biological Sciences, University of Essex, Colchester, UK.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ottaviani
authors.forename: Greg N
authors.initials: GN
authors.lastname: Brooke
authors.forename: Ciara
authors.initials: C
authors.lastname: O'Hanlon-Brown
authors.forename: Jonathan
authors.initials: J
authors.lastname: Waxman
authors.forename: Simak
authors.initials: S
authors.lastname: Ali
authors.forename: Laki
authors.initials: L
authors.lastname: Buluwela
mesh_terms: D000728:Androgens / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D050938:Glycine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism
chemical_list: D000728:Androgens; D011944:Receptors, Androgen; D050938:Glycine N-Methyltransferase
keywords: androgen receptor; androgen response element; glycine N-methyltransferase; prostate cancer