Straughn J Michael, Shaw Denise R, Guerrero Antonio, Bhoola Snehal M, Racelis Alicia, Wang Zhiqing, Chiriva-Internati Maurizio, Grizzle William E, Alvarez Ronald D, Lim Seah H, Strong Theresa V
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Alabama, Birmingham, AL 35294, USA.
Int J Cancer. 2004 Mar 1;108(6):805-11. doi: 10.1002/ijc.11617.
Sperm protein 17 (Sp17) is an antigenic protein highly expressed in spermatozoa. Sp17 expression was demonstrated recently in multiple myeloma, suggesting that it may be a novel cancer-testis antigen. Expression of Sp17 mRNA and protein was examined in human ovarian tumors. Sp17 mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis of RNA derived from epithelial ovarian tumors and normal tissues. RT-PCR analysis detected Sp17 transcripts in 15 of 18 (83%) primary ovarian tumors. The transcript was not detected in RNA derived from normal uterus or cervix, whereas weak expression was noted in some normal ovarian tissue samples. Northern blot analysis showed no detectable Sp17 mRNA expression in normal tissues, including normal ovary, but showed Sp17 expression in 17 of 25 ovarian tumors (68%). To evaluate protein expression, mouse monoclonal antibodies were produced against recombinant Sp17 protein and used in Western blot and immunohistochemical analyses of normal reproductive tissue and primary ovarian tumor samples. Sp17 protein was detected by Western blot analysis in normal spermatozoa and in 8 of 19 ovarian tumor samples. Immunohistochemical studies showed Sp17 expression in spermatozoa, ciliated cells of the female reproductive tract, and most ovarian tumors evaluated. Tumors showed a predominantly nuclear localization of Sp17 expression, with some cytoplasmic staining. These results demonstrate that Sp17, a protein with restricted expression in somatic tissues, is expressed in ovarian tumors. Because Sp17 is immunogenic, it may represent a novel target for immunotherapeutic interventions for ovarian cancer patients.
精子蛋白17(Sp17)是一种在精子中高度表达的抗原性蛋白。最近在多发性骨髓瘤中证实了Sp17的表达,这表明它可能是一种新型的癌-睾丸抗原。对人卵巢肿瘤中Sp17 mRNA和蛋白的表达进行了检测。通过逆转录-聚合酶链反应(RT-PCR)以及对来自上皮性卵巢肿瘤和正常组织的RNA进行Northern印迹分析来评估Sp17 mRNA。RT-PCR分析在18例原发性卵巢肿瘤中的15例(83%)检测到Sp17转录本。在来自正常子宫或宫颈的RNA中未检测到该转录本,而在一些正常卵巢组织样本中观察到弱表达。Northern印迹分析显示在包括正常卵巢在内的正常组织中未检测到Sp17 mRNA表达,但在25例卵巢肿瘤中的17例(68%)显示有Sp17表达。为了评估蛋白表达,制备了针对重组Sp17蛋白的小鼠单克隆抗体,并用于正常生殖组织和原发性卵巢肿瘤样本的蛋白质印迹及免疫组织化学分析。通过蛋白质印迹分析在正常精子以及19例卵巢肿瘤样本中的8例中检测到Sp17蛋白。免疫组织化学研究显示Sp17在精子、女性生殖道的纤毛细胞以及大多数评估的卵巢肿瘤中表达。肿瘤中Sp17表达主要定位于细胞核,有一些细胞质染色。这些结果表明,Sp17这种在体细胞组织中表达受限的蛋白在卵巢肿瘤中表达。由于Sp17具有免疫原性,它可能代表卵巢癌患者免疫治疗干预的一个新靶点。