Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer

Kido, Tatsuo; Schubert, Stephanie; Hatakeyama, Shingo; Οhyama, Chikara; Schmidtke, Jörg; Lau, Yun‐Fai Chris

doi:10.1186/2045-3701-4-9

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…, primarily expressed in spermatogonia and spermatocytes in the testis 128. However, when such Y-located transgene is introduced into the cancerous genetic background of the LADY prostate cancer line, the human TSPY transgene is ectopically activated gradually in foci of cancer cells in the early stages and widely expressed in late stages of prostatic oncogenesis, thereby supporting the notion that this Y-located and tandemly repeated human transgene, under its own promoter, could be activated under tumorigenic conditions 129. On the other hand, when the human TSPY gene or a TSPY promoter-directed transgene is integrated into the host autosomes,2572 the transgenes are expressed in the testis as well as various somatic tissues, particularly neurons of the central and peripheral nervous systems from E12.5 embryonic to adult stages 2572.…”

Section: Tspy and Tspx Actions Beyond Cancersmentioning

confidence: 83%

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis

Lau

Kido

2019

Asian J Androl

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The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

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Section: Tspy and Tspx Actions Beyond Cancersmentioning

confidence: 83%

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis

Lau

Kido

2019

Asian J Androl

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“…Since TSPY is tandemly repeated 30-60 times on the human Y chromosome [40], such tandem integration of the human transgene on the mouse Y chromosome resembles the organization of the human endogenous gene. Characterization of animals from this transgenic line showed that the human TSPY transgene is expressed in similar patterns as those of the human endogenous gene, including normal expression in spermatogonia and spermatocytes in the testis [62] and aberrant activation during oncogenesis [63]. Hence, TgTSPY9 is a humanized mouse model for TSPY gene.…”

Section: Of Mice and Menmentioning

confidence: 92%

Y chromosome in health and diseases

Lau

2020

Cell Biosci

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Sex differences are prevalent in normal development, physiology and disease pathogeneses. Recent studies have demonstrated that mosaic loss of Y chromosome and aberrant activation of its genes could modify the disease processes in male biased manners. This mini review discusses the nature of the genes on the human Y chromosome and identifies two general categories of genes: those sharing dosage-sensitivity functions with their X homologues and those with testis-specific expression and functions. Mosaic loss of the former disrupts the homeostasis important for the maintenance of health while aberrant activation of the latter promotes pathogenesis in non-gonadal tissues, thereby contributing to genetic predispositions to diseases in men.

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“…Samples were stained with hematoxylin-eosin (H&E). Immunofluorescence (IF) staining was performed as described [15].…”

Section: Methodsmentioning

confidence: 99%

A Novel Nanofiber Hydrogel Loaded with Platelet-Rich Plasma Promotes Wound Healing Through Enhancing the Survival of Fibroblasts

Zhang

Zhou²,

Wang³

et al. 2019

Med Sci Monit

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Background: Hydrogels are ideal biological carriers in vivo and have been widely used in the treatment of wound healing through loading with or without bioactive substances. Platelet-rich plasma (PRP) is purified from autologous plasma and has known curative efficacy for wound healing. The combined efficacy of shorten poly-N-acetyl glucosamine (sNAG) hydrogels and PRP in the treatment of wound healing has not been previously assessed. Material/Methods: The cytotoxic and proliferative effects of PRP on fibroblasts were detected using Cell Counting Kit-8 assays and flow cytometry. The levels of cyclin D1 and cyclin D3 were assessed to evaluate cell proliferation. Protein expression was assessed by western blot analysis. Adenosine levels were assessed by enzyme-linked immunosorbent assay. Cell apoptosis was assessed by flow cytometry and western blot analysis. Rat wound models were performed, and the effects of PRP, single hydrogels, and sNAG hydrogels loaded with PRP were respectively detected through the assessment of wound closure. Hematoxylin eosin staining was used to measure the depth and width of regenerative scars. Results: Our results demonstrated that PRP promotes fibroblast proliferation and inhibits apoptosis. PRP contains abundant levels of adenosine, which has a positive role on fibroblast function, whilst the inhibition of adenosine A2A receptors impairs the efficacy of PRP. sNAG hydrogels loaded with PRP showed curative efficacy during wound healing in mice. Mice treated with hydrogels loaded with PRP showed high levels of regeneration with scarless healing. Conclusions: Our results indicate that sNAG hydrogels loaded with PRP promote wound healing. The pro-proliferative, and anti-apoptotic effects of the fibroblasts are mediated by the activating A2A receptor in response to elevated adenosine levels.

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Expression of a Y-located human proto-oncogene TSPY in a transgenic mouse model of prostate cancer

Cited by 8 publications

References 57 publications

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis

Y chromosome in health and diseases

A Novel Nanofiber Hydrogel Loaded with Platelet-Rich Plasma Promotes Wound Healing Through Enhancing the Survival of Fibroblasts

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