Catalase Overexpression Induces Differential Responses in Human Amelanotic Melanoma Cells: Cell Pigmentation or Migration

BRACALENTE, C.; IBAÑEZ, I. L.; SALGUERO, N.; NOTCOVICH, C.; MULLER, C.; LISBOA DA MOTTA, L.; KLAMT, F.; DURÁN, H.

Buenos Aires

Congreso; VIII Meeting of the South American Group of the Society for Free Radical Biology and Medicine (SFRBM); 2013

South American Group of the Society for Free Radical Biology and Medicine (SFRBM)

Melanoma arises from malignant melanocyte transformation and advanced melanoma is characterized by loss of pigmentation. H2O2 participates in proliferation and differentiation. Thus, high levels of H2O2 described in melanoma cells might result in amelanotic malignant melanoma. To assess H2O2 involvement in this phenotype, a catalase overexpression model by stable transfection of A375 human melanoma cells with human catalase cDNA was generated. Three clones were obtained: A7, G10 and C10 and characterized by its greater catalase activity and expression, lower intracellular levels of  H2O2 and lower proliferation respect to controls (p <0.05). Besides, decrease in ERK and AKT activation (p <0.05) was observed. G10 showed increased migration capacity and cofilin expression and A7 showed increased melanin synthesis, TYRP1 expression and UV tolerance vs controls (p <0.05). In-vivo tumorigenicity was evaluated and differential responses were obtained. C10 was not tumorigenic (p <0.01) and G10 presented very low tumorigenicity (p <0.05) vs controls. A7 induced tumors comparable to controls but showed melanin pigmentation as observed in-vitro. Analysis of 8-OH-guanosine, cofilin and TYRP1 by IHC were performed supporting in-vitro results. Concluding, compensatory mechanisms induced by catalase overexpression inhibit proliferation and tumorigenesis but induces differential responses as differentiation or migration.