IN VITRO STUDY OF THE ROLE OF VAV PROTEINS IN MELANOMA

NAHUEL CESATTI LALUCE; MAMBERTO MACARENA; GUERCETTI JUALIAN; ANSELMINO LUCIANO; MALIZIA FLORENCIA; GIRARDINI JAVIER; MAURICIO MENACHO MÁRQUEZ

Mar del Plata

Congreso; Reunión Anual de Biociencia 2019; 2019

Sociedad Argentina de Investigación Clínica (SAIC)

Melanoma is the most dangerous form ofskin cancer, accounting for the third highest number of lives lostacross all cancers. Since the incidence of melanoma is steadilyincreasing in the population, finding prognostic and therapeutictargets appears a crucial task. Vav proteins are guanosinenucleotide exchange factors (GEFs) of the Rho GTPase family. AsGEFs, they modulate processes highly associated to thedevelopment of cancer and metastasis, mostly through theirGTPase regulatory function, but their involvement in melanomais yet to be elucidated. Previous results of our groupdemonstrated by in vitro studies a role for Vav2 in melanomacells proliferation and migration. To further explore the role ofthis protein in melanoma development, we performed in vivoexperiments. Using shRNA techniques and transfection wit expression vectors, we modulated Vav2 expression or activity inB16-F0 melanoma cell lines. These cells (2x105 cells/100 μL)were subcutaneously injected in the right flank of 8 weeks-oldC57Bl6 female mice (n= 7-9/group). Tumor volume wasmeasured with a calliper biweekly during 3 weeks. At the end ofthe experiment mice were sacrificed to collect tumor samplesand lungs. Growth kinetics indicated that tumors with reducedexpression of Vav2 grow slowly than the control (doubling time1.71 ± 0.08 versus 1.53 ± 0.11; p