title: Role of SOCS-1 Gene on Melanoma Cell Growth and Tumor Development.
abstract: 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.
authors: Experimental Oncology Unit, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, São Paulo, SP, Brazil.
authors: Jorge A Borin
authors: JA
authors: Scutti
authors: Alisson Leonardo
authors: AL
authors: Matsuo
authors: Felipe Valença
authors: FV
authors: Pereira
authors: Mariana Hiromi
authors: MH
authors: Massaoka
authors: Carlos Rogério
authors: CR
authors: Figueiredo
authors: Dayson Friaça
authors: DF
authors: Moreira
authors: José Ernesto
authors: JE
authors: Belizário
authors: Luiz R
authors: LR
authors: Travassos