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

Autor(es)

Borin Scutti, Jorge A. ^[1] ; Matsuo, Alisson Leonardo ^[1] ; Pereira, Felipe Valenca ^[1] ; Massaoka, Mariana Hiromi ^[1] ; Figueiredo, Carlos Rogerio ^[1] ; Moreira, Dayson Friaca ^[2] ; Belizario, Jose Ernesto ^[2] ; Travassos, Luiz R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Unidade Oncol Expt, BR-04023062 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: TRANSLATIONAL ONCOLOGY; v. 4, n. 2, p. 101-109, APR 2011.
• Citações Web of Science: 17

Resumo

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. (AU)

• Processo FAPESP: 06/50634-2 - Peptídeos e peptidases: atividades biológicas em doenças infecciosas e câncer
• Beneficiário: Luiz Rodolpho Raja Gabaglia Travassos
• Modalidade de apoio: Auxílio à Pesquisa - Temático