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.