Significance of aberrant β-microseminoprotein expression in prostate cancer

1.为探讨β-微球蛋白（β-MSP/PSP 94）基因在前列腺癌中的异常表达及其意义，我们设计了一种特异性针对β-MSP/PSP 94（PSP 57）mRNA的寡核苷酸探针，应用原位杂交技术检测了前列腺癌细胞（PC-3、LNCaP和DU-145）和癌组织中PSP 57 mRNA的表达。在前列腺活检组织中未观察到PSP 57 mRNA的表达，而在LNCaP细胞中观察到PSP 57 mRNA的表达。提示PSP 57 mRNA表达可能无临床意义.我们对小鼠β-MSP/PSP 94基因进行了cDNA和基因组克隆，发现了β-MSP/PSP 94在不同物种中的几个高度保守特征。本研究采用RT-PCR和原位杂交技术研究了β-MSP/PSP 94基因在啮齿类动物不同组织中的表达及其组织分布。基因表达仅在前列腺中发现.我们制备了抗大鼠β-MSP/PSP 94的多克隆兔抗体。我们发现β-MSP/PSP 94主要定位于大鼠前列腺中，并且在大鼠前列腺的不同叶中有不同水平的表达，仅在外侧叶中有显著水平的表达.在与PSA的对比研究中，我们观察了雄激素剥夺治疗后β-MSP/PSP 94的表达。与PSA相比，在雄激素剥夺治疗下，良性前列腺中β-MSP/PSP 94的表达持续存在。在高级别肿瘤中，β-MSP/PSP 94的合成似乎在雄激素刺激缺乏时被激活，这表明β-MSP/PSP 94的调节可能存在替代途径。我们用大鼠probasin（rPB）研究了β-MSP/PSP 94的基因表达，rPB是一种典型的基因应答6。雄激素调节β-MSP/PSP 94基因在转录水平上的表达对前列腺背外侧的特异性高于rPB，因此对雄激素消融的敏感性较低。这可能对癌症治疗中靶向前列腺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.