TPSY
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.
TSPY is a member of the TSPY/SET/NAP1 superfamily and harbors a highly conserved domain, termed SET/NAP domain.
The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein. (#18649364#)
The gonadoblastoma (GBY) locus is the only oncogenic locus on the human Y chromosome. It is postulated to serve a normal function in the testis, but could exert oncogenic effects in dysgenetic gonads of individuals with intersex and/or dysfunctional testicular phenotypes.
The testis-specific protein Y-encoded (TSPY) gene could be the putative gene for GBY.
TSPY serves normal functions in male stem germ cell proliferation and differentiation, but is ectopically expressed in early and late stages of gonadoblastomas, testicular carcinoma in situ (the premalignant precursor for all testicular germ cell tumors), seminomas, and selected nonseminomas.
Aberrant TSPY expression stimulates protein synthetic activities, accelerates cell proliferation, and promotes tumorigenicity in athymic mice. - TSPY binds to type B cyclins, enhances an activated cyclin B-CDK1 kinase activity, and propels a rapid G(2)/M transition in the cell cycle.
TSPY also counteracts the normal functions of its X-homologue, TSPX, which also binds to cyclin B and modulates the cyclin B-CDK1 activity to insure a proper G(2)/M transition in the cell cycle.
Hence, ectopic expression and actions of the Y-located TSPY gene in incompatible germ cells, such as those in dysgenetic or ovarian environments and dysfunctional testis, disrupt the normal cell cycle regulation and predispose the host cells to tumorigenesis.
The contrasting properties of TSPY and TSPX suggest that somatic cancers, such as intracranial germ cell tumors, melanoma, and hepatocellular carcinoma, with detectable TSPY expression could exhibit sexual dimorphisms in the initiation and/or progression of the respective oncogenesis.
TSPY is preferentially expressed in tumor germ cells of all gonadoblastoma specimens.
TSPY is abundantly expressed in all stages of these germ cell tumors.
TSPY may either be involved in the oncogenesis of or be a useful marker for both types of germ cell tumors.
GBY locus
The gonadoblastoma locus on the Y chromosome (GBY) predisposes the dysgenetic gonads of XY females to develop in situ tumors.
GBY has been mapped to a critical interval on the short arm and adjacent centromeric region on the Y chromosome.
Currently there are five functional genes identified on the GBY critical region, thereby providing likely candidates for this cancer predisposition locus.
Pathology
The testis-specific protein Y-encoded (TSPY) gene is the putative gene for the gonadoblastoma locus on the Y chromosome (GBY) that predisposes dysgenetic gonads of intersex patients to gonadoblastoma development.
TSPY is expressed at high levels in gonadoblastoma tissues, supporting its possible oncogenic function in this type of germ cell tumors.
TSPY, in combination with other markers, could be an important marker for diagnosis and subclassification of TGCTs and support its role in the pathogenesis of both gonadoblastoma and TGCTs. (#17521702#)
Open access references
The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors. Li Y, Tabatabai ZL, Lee TL, Hatakeyama S, Ohyama C, Chan WY, Looijenga LH, Lau YF. Hum Pathol. 2007 Oct;38(10):1470-81. PMID: #17521702# (Free)
References
Gonadoblastoma locus and the TSPY gene on the human Y chromosome. Lau YF, Li Y, Kido T. Birth Defects Res C Embryo Today. 2009 Mar;87(1):114-22. Review. PMID: #19306348#
Expression of a candidate gene for the gonadoblastoma locus in gonadoblastoma and testicular seminoma. Lau Y, Chou P, Iezzoni J, Alonzo J, Kömüves L. Cytogenet Cell Genet. 2000;91(1-4):160-4. PMID: #11173850#