Pathobiological properties of the ubiquitin ligase N edd4 L in melanoma

Summary A recent global gene expression profiling study unexpectedly showed that activated oncogenic NRAS may recruit neural precursor cell expressed, developmentally downregulated 4 L ( N edd4 L ; a human homologue of N edd4‐2) in cultured melanoma cells. However, whether N edd4 L was expressed in melanoma tissues or participated in melanoma carcinogenesis remains to be clarified. Here, we investigated the expression status of N edd4 L in human melanocytes, benign nevi and melanoma tissue specimens and subsequently attempted to determine the role of N edd4 L in melanoma cell growth. Immunohistochemical staining revealed that N edd4 L was not present in any non‐tumorous melanocytes or in 18 benign nevi tissues, but it was detected in 34 of 79 cutaneous melanomas and 9 of 32 nodal metastatic melanomas. Downregulation of N edd4 L significantly reduced the growth of cultured G 361 melanoma cells in vitro . Moreover, exogenous N edd4 L expression significantly promoted the growth of A 2058 melanoma cells in vivo in a xenograft assay. The present findings indicate that N edd4 L expression may be increased to facilitate tumour growth in many melanomas.