Significance of aberrant β-microseminoprotein expression in prostate cancer

1.为明确前列腺癌组织中异常β-MSP/PSP94基因表达的意义，我们设计了针对异常β-MSP/PSP94(β-MSP/PSP94)基因的寡核苷酸探针，用原位杂交方法检测了前列腺癌PC-3、LNCaP、DU-145细胞及癌组织中PSP57mRNA的表达。PSP57mRNA在LNCaP细胞中有表达，而在前列腺活检组织中未见表达。这些结果提示PSP57mRNA的表达可能没有临床意义。我们对小鼠β-MSP/PSP94基因进行了基因克隆，发现β-MSP/PSP94在不同物种间具有高度保守的特性。采用RT-PCR法和原位杂交法研究了β-MSP/PSP94基因在不同组织中的表达及其在组织中的分布。基因只在前列腺组织中表达。我们制备了抗大鼠β-MSP/PSP94的兔多克隆抗体。我们发现β-MSP/PSP94主要定位于大鼠前列腺，β-MSP/PSP94在大鼠前列腺不同叶中表达水平不同，仅在侧叶中检测到显著水平。β-MSP/PSP94在去雄激素治疗后的表达与PSA进行了对比研究，β-MSP/PSP94在良性前列腺组织中的表达在雄激素缺乏时持续存在，而在高级别肿瘤中β-MSP/PSP94的合成在没有雄激素刺激的情况下似乎被激活了，这表明在调节β-MSP/PSP94.5的过程中可能存在其他途径。我们研究了β-MSP/PSP94的基因表达与大鼠前盆(Rpb)，一个典型的响应基因。对雄激素的调节。β-MSP/PSP94基因在转录水平的表达比RPB更具特异性，因此对雄激素消融的敏感性较低。这可能对癌症治疗中以前列腺癌为靶点的策略具有临床意义。

1. To clarify the significance of aberrant β-microseminoprotein (β-MSP/PSP94) gene expression in prostate cancer, we designed an oligo-DNA probe specific to aberrant β-MSP/PSP94 (PSP57) mRNA.We investigated the expression of PSP57 mRNA in prostate cancer cells (PC-3, LNCaP and DU-145) and cancerous tissues by in situ hybridization method. PSP57 mRNA expression was observed in LNCaP cells but not in prostate biopsy tissues. These results suggest that PSP57 mRNA expression may not be clinically significant.2. We performed cDNA and genomic cloning of mouse β-MSP/PSP94 gene, and found several highly conserved characteristics of β-MSP/PSP94 among different species. We investigated the gene expression of β-MSP/PSP94 and its tissue distribution in various rodent tissues by RT-PCR and in situ hybridization. Gene expression was found only in the prostate.3. We generated a polyclonal rabbit antibody against rat β-MSP/PSP94. We found that β-MSP/PSP94 was located primarily in rat prostate and that β-MSP/PSP94 is present at different levels in different lobes of rat prostate, with significant levels detectable only in the lateral lobe.4. β-MSP/PSP94 expression after androgen deprivation therapy was investigated in a comparative study with PSA.β-MSP/PSP94 expression in benign prostate persists under androgen deprivation compared to PSA.β-MSP/PSP94 synthesis in high grade tumor appears to be activated in the absence of androgen stimulation, indicating the possible alternative pathways in the regulation of β-MSP/PSP94.5. We studied the gene expression of β-MSP/PSP94 with rat probasin (rPB), a gene typically responsive6. to androgen regulation. β-MSP/PSP94 gene expression at the transcriptional level is more specific to the dorsolateral prostate than rPB and thus less sensitive to androgen ablation. This may have clinical implications for strategies to target the prostate in cancer therapy.