Role of SOCS-1 Gene on Melanoma Cell Growth and Tumor Development

• Autor(a) principal: Borin Scutti, Jorge Augusto [UNIFESP]
• Data de Publicação: 2011
• Outros Autores: Matsuo, Alisson Leonardo [UNIFESP], Pereira, Felipe Valença [UNIFESP], Massaoka, Mariana Hiromi [UNIFESP], Figueiredo, Carlos Rogerio [UNIFESP], Moreira, Dayson Friaca, Belizario, Jose Ernesto, Travassos, Luiz Rodolpho [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1593/tlo.10250; http://repositorio.unifesp.br/handle/11600/33578

Melanoma is the most aggressive form of skin cancer, and its incidence has increased dramatically over the years. the murine B16F10 melanoma in syngeneic C57Bl/6 mice has been used as a highly aggressive model to investigate tumor development. Presently, we demonstrate in the B16F10-Nex2 subclone that silencing of SOCS-1, a negative regulator of Jak/Stat pathway, leads to reversal of the tumorigenic phenotype and inhibition of melanoma cell metastasis. SOCS-1 silencing with short hairpin RNA affected tumor growth and cell cycle regulation with arrest at the S phase with large-sized nuclei, reduced cell motility, and decreased melanoma cell invasion through Matrigel. A clonogenic assay showed that SOCS-1 acted as a modulator of resistance to anoikis. in addition, down-regulation of SOCS-1 decreased the expression of epidermal growth factor receptor ( mainly the phosphorylated-R), Ins-R alpha, and fibroblast growth factor receptor. in vivo, silencing of SOCS-1 inhibited subcutaneous tumor growth and metastatic development in the lungs. Because SOCS-1 is expressed in most melanoma cell lines and bears a relation with tumor invasion, thickness, and stage of disease, the present results on the effects of SOCS-1 silencing in melanoma suggest that this regulating protein can be a target of cancer therapy.