Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The contribution of specific genes on the Y chromosome in the etiology of prostate cancer has been undefined. Genetic mapping studies have identified a gonadoblastoma locus on the human Y chromosome (GBY) that predisposes the dysgenetic gonads of XY sex-reversed patients to tumorigenesis. Recently a candidate gene, the testis-specific protein Y-encoded (TSPY) that resides on the GBY critical region, has been demonstrated to express preferentially in tumor cells in gonadoblastoma and testicular germ cell tumors. TSPY shares high homology to a family of cyclin B binding proteins and has been considered to possibly play a role in cell cycle regulation or cell division. To address the possible involvement of the TSPY gene in prostate cancer, both in situ mRNA hybridization and immunohistochemistry techniques were used to study the expression of this putative GBY gene in prostate specimens. Our results demonstrated that TSPY was expressed at low levels in normal epithelial cells and benign prostatic hyperplasia (BPH), but at elevated levels in tumor cells of prostate cancers at various degrees of malignancy. Sequence analysis of RT-PCR products obtained from both prostatic and testicular tissues using specific primers flanking the open reading frame of the TSPY mRNA revealed a complex pattern of RNA processing of the TSPY transcripts involving cryptic intron splicing and/or intron skipping. The variant transcripts encode a variety of polymorphic isoforms or shortened versions of the TSPY protein, some of which might possess different biochemical and/or functional properties. The abbreviated transcripts were more abundant in prostatic cancer tissues than the testicular ones. Although the exact nature of such variant TSPY transcripts and proteins is still unclear, their differential expression suggests that the TSPY gene may also be involved in the multi-step prostatic oncogenesis besides its putative role in gonadoblastoma and testicular seminoma.
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PMID:Expression pattern of a gonadoblastoma candidate gene suggests a role of the Y chromosome in prostate cancer. 1468 91

TSPY (testis-specific protein, Y-encoded) is a member of the greater SET/NAP family of molecules with various functions, e.g., in chromatin remodeling, regulation of gene expression, and has been implicated to play a role in the malignant development of gonadoblastoma, testicular and prostate cancer. Here we demonstrate that the C-terminus has a functional role for the nucleo-cytoplasmatic shuttling of the TSPY protein. Using various combinations of in vitro mutagenesis and enhanced green fluorescent protein reporter gene-expression experiments we were able to show that while the deletion of C-terminus leads to a decreased stability and enhanced degradation of the protein, the selective mutation of a C-terminal CK2 phosphorylation site (T300) prevents the TSPY protein from entering the nucleus. We conclude that phosphorylation of the (T300) residue is a necessary and functional prerequisite for TSPY's transport into the nucleus reminding of comparable data from a related Drosophila molecule, NAP1.
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PMID:CK2-dependent C-terminal phosphorylation at T300 directs the nuclear transport of TSPY protein. 1642 76

Testis-specific protein Y-encoded (TSPY) is the putative gene for the gonadoblastoma locus on the Y chromosome. TSPY is expressed in normal germ cells of fetal and adult testis and ectopically in tumor germ cells, including gonadoblastoma in intersex patients, testicular germ cell tumors, prostate cancer and other somatic cancers. It is a member of the TSPY/SET/NAP1 superfamily and harbors a highly conserved domain, termed SET/NAP domain. To explore its possible role(s) in tumorigenesis, we had performed a yeast two-hybrid screen of a fetal gonadal cDNA library and identified the translation elongation factor eEF1A as a binding partner for TSPY at the SET/NAP domain. TSPY and eEF1A were highly expressed and colocalized in tumor germ cells of human seminoma specimens, suggesting their possible interaction in germ cell tumors. They were colocalized in the cytoplasm and could be co-immunoprecipitated from transfected COS7 cells. Significantly, both eEF1A1 and eEF1A2 have postulated to be involved in various types of human cancer, including breast and prostate cancers. TSPY enhanced protein synthesis of a reporter gene, which was augmented by an overexpression of eEF1A. TSPY also increased the nuclear redistribution of eEF1A, resulting in a parallel increase in reporter gene transcripts. Our results suggest that TSPY could exert its oncogenic function(s) by interacting with eEF1As and stimulating gene expression via its enhancements in protein synthesis and gene transcription.
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PMID:The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein. 1864 64

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.
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PMID:The Y-located gonadoblastoma gene TSPY amplifies its own expression through a positive feedback loop in prostate cancer cells. 2458 32

The gonadoblastoma gene, testis-specific protein Y-encoded (TSPY), on the Y chromosome and its X-homologue, TSPX, are cell cycle regulators and function as a proto-oncogene and a tumor suppressor respectively in human oncogenesis. TSPY and TSPX competitively bind to the androgen receptor (AR) and AR variants, such as AR-V7, at their conserved SET/NAP domain, and exacerbate and repress the transactivation of the AR/AR-V7 target genes in ligand dependent and independent manners respectively. The inhibitory domain has been mapped to the carboxyl acidic domain of TSPX, truncation of which renders TSPX to be stimulatory while its transposition to the C-terminus of TSPY results in an inhibitory hybrid protein. TSPY and TSPX co-localize with the endogenous AR, in the presence of ligand, on the promoters and differentially regulate the expression of the endogenous AR target genes in the androgen-responsive LNCaP prostate cancer cells. Transcriptome analysis shows that TSPY and TSPX expressions differentially affect significant numbers of canonical pathways, upstream regulators and cellular functions. Significantly, among the common ones, TSPY activates and TSPX inhibits numerous growth-related and oncogenic canonical pathways and cellular functions in the respective cell populations. Hence, TSPY and TSPX exert opposing effects on the transactivation functions of AR and AR-Vs important for various physiological and disease processes sensitive to male sex hormone actions, thereby not only affecting the pathogenesis of male-specific prostate cancer but also likely contributing to sex differences in the health and diseases of man.
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PMID:The Y-located proto-oncogene TSPY exacerbates and its X-homologue TSPX inhibits transactivation functions of androgen receptor and its constitutively active variants. 2816 98