Büscher Kristina, Trefzer Uwe, Hofmann Maja, Sterry Wolfram, Kurth Reinhard, Denner Joachim
Robert Koch-Institute and Department of Dermatology, Campus Charité-Mitte, Charité-University Medicine Berlin, Berlin, Germany.
Cancer Res. 2005 May 15;65(10):4172-80. doi: 10.1158/0008-5472.CAN-04-2983.
The human endogenous retrovirus K family (HERV-K) comprises 30 to 50 closely related proviruses, most of which are defective. In contrast to all other human endogenous retroviruses, some HERV-K proviruses have maintained open reading frames for all viral proteins. In addition to the structural proteins Gag and Env and the reverse transcriptase, two regulatory proteins (Rec and Np9) have been described. Malignant melanoma has the highest mortality among skin cancers and is particularly aggressive. To study the expression of HERV-K, a set of seven primers was developed that allows discrimination between full-length and spliced mRNA and mRNA from deleted and undeleted proviruses. Expression of full-length mRNA from deleted and undeleted proviruses was detected in all human cells investigated. Expression of spliced env and rec was detected in a teratocarcinoma cell line, in 45% of the metastatic melanoma biopsies, and in 44% of the melanoma cell lines. In normal neonatal melanocytes, spliced rec was detected but not spliced env. Viral proteins were shown to be expressed in primary melanomas, metastases, and melanoma cell lines by immunohistochemistry, immunofluorescence, and Western blot analyses using specific antisera. For the first time, antibodies against HERV-K were found in melanoma patients. Melanomas are, in addition to teratocarcinomas and human breast cancer, the third tumor type with enhanced expression of HERV-K.
人类内源性逆转录病毒K家族（HERV-K）由30至50种密切相关的前病毒组成，其中大多数是有缺陷的。与所有其他人类内源性逆转录病毒不同，一些HERV-K前病毒保留了所有病毒蛋白的开放阅读框。除了结构蛋白Gag和Env以及逆转录酶外，还描述了两种调节蛋白（Rec和Np9）。恶性黑色素瘤在皮肤癌中死亡率最高，且具有特别强的侵袭性。为了研究HERV-K的表达，开发了一组七条引物，可区分全长和剪接的mRNA以及来自缺失和未缺失前病毒的mRNA。在所有研究的人类细胞中均检测到来自缺失和未缺失前病毒的全长mRNA的表达。在一个畸胎瘤细胞系、45%的转移性黑色素瘤活检样本以及44%的黑色素瘤细胞系中检测到了剪接的env和rec的表达。在正常新生儿黑素细胞中，检测到了剪接的rec，但未检测到剪接的env。通过使用特异性抗血清的免疫组织化学、免疫荧光和蛋白质印迹分析表明，病毒蛋白在原发性黑色素瘤、转移灶和黑色素瘤细胞系中表达。首次在黑色素瘤患者中发现了针对HERV-K的抗体。除畸胎瘤和人类乳腺癌外，黑色素瘤是第三种HERV-K表达增强的肿瘤类型。
