Expression pattern of a gonadoblastoma candidate gene suggests a role of the Y chromosome in prostate cancer.

The contribution of specific genes on the Y chromosome in the etiology of prostate cancer has been undefined. Genetic mapping studies have identified a gonadoblastoma locus on the human Y chromosome (GBY) that predisposes the dysgenetic gonads of XY sex-reversed patients to tumorigenesis. Recently a candidate gene, the testis-specific protein Y-encoded (TSPY) that resides on the GBY critical region, has been demonstrated to express preferentially in tumor cells in gonadoblastoma and testicular germ cell tumors. TSPY shares high homology to a family of cyclin B binding proteins and has been considered to possibly play a role in cell cycle regulation or cell division. To address the possible involvement of the TSPY gene in prostate cancer, both in situ mRNA hybridization and immunohistochemistry techniques were used to study the expression of this putative GBY gene in prostate specimens. Our results demonstrated that TSPY was expressed at low levels in normal epithelial cells and benign prostatic hyperplasia (BPH), but at elevated levels in tumor cells of prostate cancers at various degrees of malignancy. Sequence analysis of RT-PCR products obtained from both prostatic and testicular tissues using specific primers flanking the open reading frame of the TSPY mRNA revealed a complex pattern of RNA processing of the TSPY transcripts involving cryptic intron splicing and/or intron skipping. The variant transcripts encode a variety of polymorphic isoforms or shortened versions of the TSPY protein, some of which might possess different biochemical and/or functional properties. The abbreviated transcripts were more abundant in prostatic cancer tissues than the testicular ones. Although the exact nature of such variant TSPY transcripts and proteins is still unclear, their differential expression suggests that the TSPY gene may also be involved in the multi-step prostatic oncogenesis besides its putative role in gonadoblastoma and testicular seminoma.