The Y-encoded TSPY protein: a significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors.
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.
Li
Yunmin
Y
Department of Medicine, VA Medical Center, University of California, San Francisco, CA 94121, USA.
Tabatabai
Z Laura
ZL
Lee
Tin-Lap
TL
Hatakeyama
Shingo
S
Ohyama
Chikara
C
Chan
Wai-Yee
WY
Looijenga
Leendert H J
LH
Lau
Yun-Fai Chris
YF
D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C497749:TSPY1 protein, human