The Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19891-6. doi: 10.1073/pnas.1010307107. Epub 2010 Nov 1.
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.
Y 染色体上的睾丸特异性蛋白（TSPY）是 Y 染色体上的一个扩增基因，其与性腺母细胞瘤的遗传相互作用已在临床上得到证实。然而，TSPY 蛋白在生理和病理环境下的功能仍有待表征。在本研究中，我们观察到 TSPY 和雄激素受体（AR）在患者的睾丸生殖细胞肿瘤（TGCTs）以及模型细胞系中共同表达，但在人类或小鼠的正常睾丸中未观察到这种共表达。由于 TSPY 可以捕获细胞质中的 AR，即使存在雄激素，它也是雄激素信号的抑制剂。雄激素处理刺激 TGCT 模型细胞系的细胞增殖，而 TSPY 强烈减弱了雄激素依赖性细胞生长。结合 TSPY 在体内更恶性 TGCT 中表达降低的发现，本研究表明 TSPY 作为一种抑制剂在 TGCT 中的雄激素诱导的肿瘤发展中起作用，并提出了 TSPY 可作为临床标志物用于评估 TGCT 恶性程度的可能性。
