title: Androgen regulation of the human ornithine decarboxylase promoter in prostate cancer cells.
abstract: We studied the response of the human ornithine decarboxylase (ODC) promoter to androgen in human prostate cancer cell lines. In the well-differentiated, androgen-sensitive human prostate cancer line LNCaP, a genomic ODC promoter fragment that includes putative androgen response elements was suppressed by androgen. In contrast, the androgen-regulated probasin promoter was induced by androgens. The ODC promoter was also induced by cotransfected androgen receptor in the poorly differentiated, androgen-insensitive human prostate cancer cell line PPC-1. We examined the effects of cotransfected mutant androgen receptors containing the LNCaP mutation or DNA-binding mutations. All cotransfected androgen receptors switched the ODC androgen response from suppression to induction in LNCaP cells. Gel-shift and DNA footprint assays demonstrated androgen receptor binding to an ODC sequence that does not contain a consensus androgen response element. Deletion of the sequence abolished androgen suppression of the ODC promoter. We propose a model of pleiotropic gene regulation by androgen that requires a regulatory balance between androgen receptor and a transcription factor binding to the nonconsensus androgen response element.
authors.affiliation: Department of Urology, University of Miami School of Medicine, Florida 33125, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bai
authors.forename: S
authors.initials: S
authors.lastname: Kasper
authors.forename: R J
authors.initials: RJ
authors.lastname: Matusik
authors.forename: P S
authors.initials: PS
authors.lastname: Rennie
authors.forename: J A
authors.initials: JA
authors.lastname: Moshier
authors.forename: A
authors.initials: A
authors.lastname: Krongrad
mesh_terms: D000728:Androgens / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D018983:DNA Footprinting; D004285:Dogs; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000728:Androgens; D065108:Ornithine Decarboxylase Inhibitors; D011944:Receptors, Androgen; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase