Li Yunmin, Tabatabai Z Laura, Lee Tin-Lap, Hatakeyama Shingo, Ohyama Chikara, Chan Wai-Yee, Looijenga Leendert H J, Lau Yun-Fai Chris
Department of Medicine, VA Medical Center, University of California, San Francisco, CA 94121, USA.
Hum Pathol. 2007 Oct;38(10):1470-81. doi: 10.1016/j.humpath.2007.03.011. Epub 2007 May 22.
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. To explore the possibility that this Y chromosome gene is also involved in pathogenesis of the more common testicular germ cell tumors (TGCTs), we have conducted various expression studies using immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction analysis on 171 cases of TGCTs and selected normal testis controls. Our results demonstrated that TSPY protein is abundantly expressed in the precursor, carcinoma in situ or intratubular germ cell neoplasia unclassified, and seminoma, but only minimally or not expressed in various types of nonseminomas. TSPY coexpresses with established germ cell tumor markers (such as placental-like alkaline phosphatase, c-KIT, OCT4) and proliferative markers (such as Ki-67 and cyclin B1) in the same tumor cells at both RNA and protein levels. Ectopic TSPY expression in cultured cells up-regulates progrowth genes, including those at chromosome 12p13, frequently gained/amplified in TGCTs. Our results suggest that 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.
睾丸特异性蛋白Y编码（TSPY）基因是Y染色体上性腺母细胞瘤位点（GBY）的推定基因，该基因使两性畸形患者发育异常的性腺易发生性腺母细胞瘤。TSPY在性腺母细胞瘤组织中高水平表达，支持其在这类生殖细胞肿瘤中可能的致癌功能。为了探究这个Y染色体基因是否也参与更常见的睾丸生殖细胞肿瘤（TGCT）的发病机制，我们对171例TGCT病例和选定的正常睾丸对照进行了各种表达研究，采用免疫组织化学、蛋白质印迹法以及逆转录-聚合酶链反应分析。我们的结果表明，TSPY蛋白在前体、原位癌或未分类的管内生殖细胞瘤以及精原细胞瘤中大量表达，但在各种类型的非精原细胞瘤中仅微量表达或不表达。在RNA和蛋白质水平上，TSPY在同一肿瘤细胞中与已确定的生殖细胞肿瘤标志物（如胎盘样碱性磷酸酶、c-KIT、OCT4）和增殖标志物（如Ki-67和细胞周期蛋白B1）共表达。在培养细胞中异位表达TSPY会上调促进生长的基因，包括那些在TGCT中经常获得/扩增的位于12号染色体p13区域的基因。我们的结果表明，TSPY与其他标志物结合，可能成为TGCT诊断和亚分类的重要标志物，并支持其在性腺母细胞瘤和TGCT发病机制中的作用。
