title: Transcriptional regulation of type 11 17β-hydroxysteroid dehydrogenase expression in prostate cancer cells.
abstract: Type 11 hydroxysteroid (17-beta) dehydrogenase (HSD17B11) catalyzes the conversion of 5α-androstan-3α,17β-diol into androsterone suggesting that it may play an important role in androgen metabolism. We previously described that overexpression of C/EBPα or C/EBPβ induced HSD17B11 expression in HepG2 cells but this process was not mediated by the CCAAT boxes located within its proximal promoter region. Here, we study HSD17B11 transcriptional regulation in prostate cancer (PC) cells. Transfection experiments showed that the region -107/+18 is sufficient for promoter activity in PC cells. Mutagenesis analysis indicated that Sp1 and C/EBP binding sites found in this region are essential for promoter activity. Additional experiments demonstrated that ectopic expression of Sp1 and C/EBPα upregulated HSD17B11 expression only in PC cell lines. Through DAPA and ChIP assays, specific recruitment of Sp1 and C/EBPα to the HSD17B11 promoter was detected. These results show that HSD17B11 transcription in PC cells is regulated by Sp1 and C/EBPα.
authors.affiliation: Department of Health Sciences, Universidad Pública de Navarra, Avda. Barañain, 31008 Pamplona, Spain.
authors.forename: Mirja
authors.initials: M
authors.lastname: Rotinen
authors.forename: Joaquín
authors.initials: J
authors.lastname: Villar
authors.forename: Jon
authors.initials: J
authors.lastname: Celay
authors.forename: Irantzu
authors.initials: I
authors.lastname: Serrano
authors.forename: Vicente
authors.initials: V
authors.lastname: Notario
authors.forename: Ignacio
authors.initials: I
authors.lastname: Encío
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D020121:5' Untranslated Regions / Q000235:genetics; D000445:Aldehyde Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D022763:CCAAT-Enhancer-Binding Protein-alpha; D011994:Recombinant Proteins; D016329:Sp1 Transcription Factor; D015067:17-Hydroxysteroid Dehydrogenases; C118226:HSD17B11 protein, human; D049410:Luciferases, Renilla; D000445:Aldehyde Oxidoreductases