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1.
Proc Natl Acad Sci U S A ; 107(46): 19891-6, 2010 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-21041627

RESUMEN

Testis-specific protein on Y chromosome (TSPY) is an ampliconic gene on the Y chromosome, and genetic interaction with gonadoblastoma has been clinically established. However, the function of the TSPY protein remains to be characterized in physiological and pathological settings. In the present study, we observed coexpression of TSPY and the androgen receptor (AR) in testicular germ-cell tumors (TGCTs) in patients as well as in model cell lines, but such coexpression was not seen in normal testis of humans or mice. TSPY was a repressor for androgen signaling because of its trapping of cytosolic AR even in the presence of androgen. Androgen treatment stimulated cell proliferation of a TGCT model cell line, and TSPY potently attenuated androgen-dependent cell growth. Together with the finding that TSPY expression is reduced in more malignant TGCTs in vivo, the present study suggests that TSPY serves as a repressor in androgen-induced tumor development in TGCTs and raises the possibility that TSPY could be used as a clinical marker to assess the malignancy of TGCTs.


Asunto(s)
Andrógenos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias de Células Germinales y Embrionarias/metabolismo , Receptores Androgénicos/metabolismo , Proteínas Represoras/metabolismo , Neoplasias Testiculares/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Ciclina D2/genética , Ciclina D2/metabolismo , Citoplasma/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/patología , Unión Proteica , Transporte de Proteínas , Receptores Androgénicos/genética , Proteínas Represoras/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/patología , Transcripción Genética
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