Human endogenous retroviral K element encodes fusogenic activity in melanoma cells

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.