Wang-Johanning Feng, Liu Jinsong, Rycaj Kiera, Huang Miao, Tsai Kate, Rosen Daniel G, Chen Dung-Tsa, Lu Danielle W, Barnhart Kirstin F, Johanning Gary L
Department of Veterinary Sciences and Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center, Houston, TX 78602, USA.
Int J Cancer. 2007 Jan 1;120(1):81-90. doi: 10.1002/ijc.22256.
Individual classes of human endogenous retrovirus (HERV) genes and proteins are expressed in cancer, but expression of more than one type of HERV is rare. We report here the expression of multiple HERV genes and proteins in ovarian cell lines and tissues. Expression of HERV-K env mRNA was greater in ovarian epithelial tumors than in normal ovarian tissues (N = 254). The expression of this protein on the surface and in the cytoplasm of ovarian cancer cells was confirmed using anti-HERV-K specific antibody by flow cytometric analysis. The frequency of expression of HERV-K env protein in multitissue microarrays (N = 641) was determined by immunohistochemistry and a significant correlation with tumor histotype was found. A significantly increased expression of HERV-K was observed in tumors with low malignant potential and low grade, relative to expression in normal ovarian tissues. The increase in expression of HERV-K env protein took place in a stepwise fashion in serous papillary adenocarcinoma. Interestingly, we found that other classes of HERV env mRNAs, including ERV3 and HERV-E, are expressed in the same ovarian cancer tissues that expressed HERV-K. Furthermore, anti-HERV antibodies including anti-ERV3 (30%), anti-HERV-E (40%) and anti-HERV-K (55%) were detected in patients with ovarian cancer, but not in normal female controls. HERV env proteins are frequently transcribed and translated in ovarian epithelial tumors, and multiple HERV families are detectable in ovarian cancer. HERV env proteins, and especially those expressed on the cell surface, may serve as novel tumor targets for detection, diagnosis and immunotherapy of ovarian cancer.
人类内源性逆转录病毒（HERV）的个别基因和蛋白类别在癌症中表达，但多种HERV的表达情况罕见。我们在此报告多种HERV基因和蛋白在卵巢细胞系及组织中的表达。HERV-K env mRNA在卵巢上皮性肿瘤中的表达高于正常卵巢组织（N = 254）。通过流式细胞术分析，使用抗HERV-K特异性抗体证实了该蛋白在卵巢癌细胞表面及细胞质中的表达。通过免疫组织化学确定了多组织微阵列（N = 641）中HERV-K env蛋白的表达频率，并发现其与肿瘤组织学类型存在显著相关性。相对于正常卵巢组织中的表达，在低恶性潜能和低级别肿瘤中观察到HERV-K的表达显著增加。在浆液性乳头状腺癌中，HERV-K env蛋白的表达呈逐步增加。有趣的是，我们发现其他HERV env mRNA类别，包括ERV3和HERV-E，在表达HERV-K的同一卵巢癌组织中表达。此外，在卵巢癌患者中检测到抗HERV抗体，包括抗ERV3（30%）、抗HERV-E（40%）和抗HERV-K（55%），而在正常女性对照中未检测到。HERV env蛋白在卵巢上皮性肿瘤中频繁转录和翻译，并且在卵巢癌中可检测到多个HERV家族。HERV env蛋白，尤其是在细胞表面表达的那些，可能成为卵巢癌检测、诊断和免疫治疗的新型肿瘤靶点。
