title: The Y-located gonadoblastoma gene TSPY amplifies its own expression through a positive feedback loop in prostate cancer cells.
abstract: The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the gonadoblastoma region of the Y chromosome, and has been considered to be the putative gene for this oncogenic locus on the male-only chromosome. It is expressed in spermatogonial cells and spermatocytes in normal human testis, but abundantly in gonadoblastoma, testicular germ cell tumors and a variety of somatic cancers, including melanoma, hepatocellular carcinoma and prostate cancer. Various studies suggest that TSPY accelerates cell proliferation and growth, and promotes tumorigenesis. In this report, we show that TSPY could bind directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the transcriptional activities of the endogenous gene in the LNCaP prostate cancer cells. Domain mapping analyses of TSPY have localized the critical and sufficient domain to the SET/NAP-domain. These results suggest that TSPY could efficiently amplify its expression and oncogenic functions through a positive feedback loop, and contribute to the overall tumorigenic processes when it is expressed in various human cancers.
authors.affiliation: Division of Cell and Developmental Genetics, Department of Medicine, Veterans Affairs Medical Center, and Institute for Human Genetics, University of California, San Francisco, CA, USA.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kido
authors.affiliation: Division of Cell and Developmental Genetics, Department of Medicine, Veterans Affairs Medical Center, and Institute for Human Genetics, University of California, San Francisco, CA, USA. Electronic address: Chris.Lau@UCSF.edu.
authors.forename: Yun-Fai Chris
authors.initials: YF
authors.lastname: Lau
mesh_terms: D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D041322:Chromosomes, Human, Y / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005091:Exons; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D018238:Gonadoblastoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025941:Protein Interaction Mapping; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; C497749:TSPY1 protein, human
keywords: Feedback loop; Gene regulation; Prostate cancer; TSPY