Human endogenous retroviral K element encodes fusogenic activity in melanoma cells

Gengming Huang1, Zhongwu Li2, Xiaohua Wan3, Yue Wang4, Jianli Dong1
1Department of Pathology; Sealy Center for Cancer Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.
2Sealy Center for Cancer Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA; Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.
3Sealy Center for Cancer Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA; Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
4The Center for Medical Genetics, Houston, TX, USA.
DOI: 10.4103/1477-3163.109032

ABSTRACT

Introduction and Hypothesis: Nuclear atypia with features of multi nuclei have been detected in human melanoma specimens. We found that the K type human endogenous retroviral element (HERV K) is expressed in such cells. Since cellular syncytia can form when cells are infected with retroviruses, we hypothesized that HERV K expressed in melanoma cells may contribute to the formation of multinuclear atypia cells in melanoma. Experiments and Results: We specifically inhibited HERV K expression using RNA interference (RNAi) and monoclonal antibodies and observed dramatic reduction of intercellular fusion of cultured melanoma cells. Importantly, we identified loss of heterozygosity (LOH)of D19S433 in a cell clone that survived and proliferated after cell fusion. Conclusion: Our results support the notion that proteins encoded by HERV K can mediate intercellular fusion of melanoma cells, which may generate multinuclear cells and drive the evolution of genetic changes that provide growth and survival advantages.

Keywords: Cell fusion, K-type human endogenous retroviral deoxyribonucleic acid, melanoma