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Role of SOCS-1 Gene on Melanoma Cell Growth and Tumor Development.
Scutti, Jorge A Borin; Matsuo, Alisson Leonardo; Pereira, Felipe Valença; Massaoka, Mariana Hiromi; Figueiredo, Carlos Rogério; Moreira, Dayson Friaça; Belizário, José Ernesto; Travassos, Luiz R.
Afiliação
  • Scutti JA; Experimental Oncology Unit, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, Brazil.
Transl Oncol ; 4(2): 101-9, 2011 Apr 01.
Article em En | MEDLINE | ID: mdl-21461173
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, downregulation of SOCS-1 decreased the expression of epidermal growth factor receptor (mainly the phosphorylated-R), Ins-Rα, 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.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Transl Oncol Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Transl Oncol Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos