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Pathobiological properties of the ubiquitin ligase N edd4 L in melanoma
Author(s) -
Kito Yusuke,
Bai Juncheng,
Goto Naoe,
Okubo Hiroshi,
Adachi Yoshihiro,
Nagayama Tomoko,
Takeuchi Tamotsu
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12051
Subject(s) - melanoma , neuroblastoma ras viral oncogene homolog , carcinogenesis , immunohistochemistry , cancer research , downregulation and upregulation , biology , ubiquitin ligase , cell growth , microbiology and biotechnology , pathology , cancer , immunology , ubiquitin , medicine , gene , genetics , colorectal cancer , kras
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.