title: Positive and negative regulation of prostate stem cell antigen expression by Yin Yang 1 in prostate epithelial cell lines.
abstract: Prostate cancer is influenced by epigenetic modification of genes involved in cancer development and progression. Increased expression of Prostate Stem Cell Antigen (PSCA) is correlated with development of malignant human prostate cancer, while studies in mouse models suggest that decreased PSCA levels promote prostate cancer metastasis. These studies suggest that PSCA has context-dependent functions, and could be differentially regulated during tumor progression. In the present study, we identified the multi-functional transcription factor Yin Yang 1 (YY1) as a modulator of PSCA expression in prostate epithelial cell lines. Increased YY1 levels are observed in prostatic intraepithelial neoplasia (PIN) and advanced disease. We show that androgen-mediated up-regulation of PSCA in prostate epithelial cell lines is dependent on YY1. We identified two direct YY1 binding sites within the PSCA promoter, and showed that the upstream site inhibited, while the downstream site, proximal to the androgen-responsive element, stimulated PSCA promoter activity. Thus, changes in PSCA expression levels in prostate cancer may at least partly be affected by cellular levels of YY1. Our results also suggest multiple roles for YY1 in prostate cancer which may contribute to disease progression by modulation of genes such as PSCA.
authors.affiliation: Molecular Pathology Graduate Program, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Shuai
authors.initials: S
authors.lastname: Tang
authors.forename: Meenu
authors.initials: M
authors.lastname: Mishra
authors.forename: Donna P
authors.initials: DP
authors.lastname: Frazier
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Moore
authors.forename: Kazushi
authors.initials: K
authors.lastname: Inoue
authors.forename: Rajendar
authors.initials: R
authors.lastname: Deora
authors.forename: Guangchao
authors.initials: G
authors.lastname: Sui
authors.forename: Purnima
authors.initials: P
authors.lastname: Dubey
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D016384:Consensus Sequence; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011119:Polynucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000166:cytology*; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism; D020218:Response Elements; D050986:YY1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D011119:Polynucleotides; D011944:Receptors, Androgen; D050986:YY1 Transcription Factor