TSPY is a cancer testis antigen expressed in human hepatocellular carcinoma

Abstract

In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that the transcription of TSPY, 'testis-specific protein Y-encoded', was upregulated in HCC. Investigation of a broad spectrum of normal and malignant tissues by RT -PCR revealed the TSPY transcript selectively expressed in normal testis, different histological types of human neoplastic tissues, and tumour cell lines. The expression of TSPY in cancer cells was further confirmed by in situ hybridisation. Indirect immunofluorescence microscopy analysis showed that TSPY was localised mainly in the cytoplasm of transiently transfected cells. Testis-specific protein Y-encoded was detected in 50% (16 of 32) of well-and moderately differentiated HCC patients, in 16% (four of 25) of poorly differentiated HCC patients, and in 5% (one of 19) of renal cell cancer patients. A serological survey revealed that 6.6% (seven of 106) HCC patients had anti-TSPY antibody response, demonstrating the immunogenicity of TSPY in humans. In conclusion, these data suggest that TSPY is a novel cancer/testis (CT) antigen and may be a potential candidate in vaccine strategy for immunotherapy in HCC patients.

TSPY and its X-encoded homologue interact with cyclin B but exert contrasting functions on cyclin-dependent kinase 1 activities

“…TSPY is ectopically expressed in tumor cells in various types of germ cell tumors, including gonadoblastoma, testicular germ cell tumors and male intracranial germ cell tumors, and has been considered as a key marker that is important in the pathogenesis of these types of human tumors Kersemaekers et al, 2005;Hoei-Hansen et al, 2006;Oram et al, 2006;Li et al, 2007b). Significantly, it is also aberrantly expressed in prostate cancer and numerous somatic cancers, including hepatocellular carcinoma and melanoma of male origins (Lau and Zhang, 2000;Lau et al, 2003;Gallagher et al, 2005;Yin et al, 2005), suggesting that the TSPY tandem arrays are hot spots for epigenetic dysregulation. Currently, the exact mechanism(s) by which TSPY exerts its putative oncogenic functions on these somatic cancers is uncertain.…”

Transcriptome analysis of hepatitis B virus-associated small hepatocellular carcinoma by serial analysis of gene expression

“…Further studies are needed to elucidate the role of ·-L-fucosidase in the screening of small HCC. TSPYL2 is homologous to testis-specific protein Yencoded (TSPY), a cancer/testis antigen which was recently reported to be expressed in 35% of HCC tissues (46). Also known as cutaneous T-cell lymphoma (CTCL)-associated tumor antigen se20-4 (47) and differentially expressed nucleolar TGF-ß1 target protein (48), TSPYL2 is elevated in the cell lines of CTCL (47), melanoma (47), leukemia (47) and non-small cell lung cancer (48).…”

The Role of the Y-Located TSPY Gene in Prostatic Oncongenesis

“…However, the precise role played by c-MYC in human prostate cancer is unclear in part due to the amplification of the 8q24 amplicon. This amplicon is particularly rich in genes, several of which [e.g., [32,[35][36][37] in a large percentage of human adenocarcinomas [38,39] and some prostate intraepithelial neoplasias (PIN) [37].…”

“…This amplicon is particularly rich in genes, several of which [e.g., c-MYC [31], NOV [nephroblastoma overexpressed gene], EIF3S3 [eukaryotic translation initiation factor 3 subunit 3], HAS2 [hyaluronan synthase2] [32], KIAA0196 [33], and PSCA [34]] are expressed in prostate and have either oncogenic or tumor suppressor potential. FISH analysis has identified amplification of the 8q24 amplicon [32,[35][36][37] in a large percentage of human adenocarcinomas [38,39] and some prostate intraepithelial neoplasias (PIN) [37].…”

“…However, the precise role played by c-MYC in human prostate cancer is unclear in part due to the amplification of the 8q24 amplicon. This amplicon is particularly rich in genes, several of which [e.g., [32,[35][36][37] in a large percentage of human adenocarcinomas [38,39] and some prostate intraepithelial neoplasias (PIN) [37].Mouse models of prostatic neoplasia have been generated in which the c-MYC gene was expressed from either the probasin promoter [20] or C(3)1 promoter [22]. Two probasin promoter variants were used in one study; these promoters share the same prostate specificity but differ in promoter activity.…”