Expression pattern of a gonadoblastoma candidate gene suggests a role of the Y chromosome in prostate cancer
Expression pattern of a gonadoblastoma candidate gene suggests a role of the Y chromosome in prostate cancer
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DOI：
10.1159/000074345
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发表时间：
2003-01-01
影响因子：
1.7
通讯作者：
Kömüves, LG
中科院分区：
文献类型：
--
作者：
Lau, YFC;Lau, HW;Kömüves, LG
Y染色体上的特定基因在前列腺癌病因学中的作用尚未明确。遗传作图研究已经确定了人类Y染色体（GBY）上的一个性腺母细胞瘤位点，该位点易使XY性别逆转患者的性腺发育不良致肿瘤发生。最近，一个位于GBY关键区域的候选基因睾丸特异性蛋白y编码（TSPY）被证明在性腺母细胞瘤和睾丸生殖细胞瘤的肿瘤细胞中优先表达。TSPY与cyclin B结合蛋白家族具有高度同源性，被认为可能在细胞周期调节或细胞分裂中发挥作用。为了解决TSPY基因在前列腺癌中的可能参与，我们使用原位mRNA杂交和免疫组织化学技术研究了该推测的GBY基因在前列腺标本中的表达。我们的研究结果表明，TSPY在正常上皮细胞和良性前列腺增生（BPH）中表达水平较低，但在不同恶性程度的前列腺癌肿瘤细胞中表达水平升高。利用TSPY mRNA开放阅读框两侧的特定引物，对从前列腺和睾丸组织获得的RT-PCR产物进行序列分析，揭示了TSPY转录本的复杂RNA加工模式，包括隐内含子剪接和/或内含子跳变。这些变异转录本编码了多种多态异构体或TSPY蛋白的缩短版本，其中一些可能具有不同的生化和/或功能特性。缩短转录本在前列腺癌组织中比在睾丸癌组织中更丰富。尽管这种TSPY基因变体的转录本和蛋白的确切性质尚不清楚，但它们的差异表达表明，TSPY基因除了在性腺母细胞瘤和睾丸精原细胞瘤中所扮演的角色外，还可能参与前列腺多步骤肿瘤的发生。版权所有(C) 2003 S. Karger AG，巴塞尔。
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. Copyright (C) 2003 S. Karger AG, Basel.