新型前列腺特异膜抗原剪接变异体的发现及临床意义初步探讨

Clinical significance of a new alternatively spliced variant of prostate specific membrane antigen

目的:探讨前列腺特异膜抗原(PSMA)及其与前列腺癌发生、发展的关系,寻求更为特异的前列腺癌诊断和治疗的靶点。方法:采用RT-PCR和DNA测序技术,克隆PSMA基因新的剪接变异体,并根据其序列信息,设计特异性引物,检测其在不同病变前列腺组织及不同组织来源肿瘤细胞中的表达。结果:发现了一种新的PS-MA剪接变异体,其在前列腺癌、前列腺增生及正常前列腺组织中的表达率分别为92.6%、78.8%及10.0%,且特异表达于前列腺癌LNCaP细胞株,而在前列腺癌PC3细胞株、膀胱癌、肾癌、肝癌细胞株中均不表达。结论:发现了一种新型PSMA剪接变异体(定名为PSMA5),并证实该变异体与前列腺癌及前列腺增生有明显相关性,为研究前列腺癌的发生机制和寻求前列腺癌特异性诊治靶点提供了新的线索。

AIM： To discuss the relationship between prostate specific membrane antigen （PSMA） and prostate cancer and to seek a target for diagnosis and therapy of prostate cancer. METHODS： A pair of primers was designed according to the published PSMA mRNA sequence. Total RNA was extracted from prostate cancer tissues and was reversely transcribed into cDNA, which was used as a template for PCR to amplify the PSMA gene. The recombinant was sequenced and the result was analyzed by BLAST. The PSMA5 gene specific primers were designed to identify its expression in different cells and prostate tissues. RESULTS： A new alternatively spliced variant of PSMA named PSMA5 was discovered when sequencing the recombinant. PSMA5 showed well pathological tissue -specificity, and its expression rate in prostate cancer, benign prostatic hyperplasia of prostate, and normal prostate tissue were 92. 6% , 78.8% and 10. 0% , respectively. It expressed specifically in Pca cell line LNCaP, not in cell lines of PC3, bladder carcinoma, renal carcinoma, or hepatoma. CONCLUSION： A new alternative spliced variant of PSMA named PSMA5 was discovered, which was well correlated with prostate cancer and benign prostatic hyperplasia. This finding may give a new clue to the evolution of prostate cancer and may provide a target for the diagnosis and therapy of prostate cancer.