BRAF INHIBITION DIMINISHES CELL VIABILITY VIA PKC ALPHA (PKCA) IN THYROID CANCER CELLS

CAMPOS HAEDO, M.N.; DIAZ FLAQUÉ, M.C.; DÍAZ ALBUJA, J.A.; PERONA, M.; DEBERNARDI, M.M.; CAYROL, M.F.; BARREIRO ARCOS, M.L.; STERLE, H.A.; JUVENAL, G.J.; CREMASCHI, G.A.; ROSEMBLIT, C.

Buenos Aires

Congreso; Reunión de Sociedades de Biociencias 2020; 2020

Sociedad Argentina de Investigación Clinica (SAIC)- Sociedad Argentina de Inmunología (SAI)- Sociedad Argentina de Fisiología (SAFIS)

Thyroid carcinoma (TC) is the most common endocrine neoplasia. Its incidence has increased in the last 40 years worldwide. It comprises a group of tumors of different lineage and biological behavior. About half of TC are driven by an acquired activating mutation in the BRAF oncogene. While targeted therapies have improved outcomes in melanoma patients, most TC patients become resistant or recur suggesting that new or additive non-cross-reactive therapies are needed. We have previously shown that PKCalpha mediates TSH and thyroid hormones proliferative effects in TC. Recent evidence indicates that together PKCalpha overexpression and BRAF mutation should contribute to tumorigenesis and resistance to anticancer therapies. We found that by inhibiting BRAF expression with RNAi in anaplastic TC cells with BRAF mutation, PKCalpha expression decreases as well, suggesting that the latter is found downstream of BRAF. Furthermore, a decrease in the expression of the cell proliferation marker PCNA was observed in BRAF-depleted cells by western blot analysis. Also, TC cells were sensitive to increasing doses of the BRAF inhibitor widely used in the clinic vemurafenib/PLX4032 in a dose-dependent manner (p