Angiotensin II, K+ and chemotherapeutic drugs increase cell resistance via ACSL4 and ABCG2 in adrenocortical carcinoma.

MAYRA AGUSTINA RIOS MEDRANO; JESICA PRADA; PAULA MALOBERTI; ANA FERNANDA CASTILLO; ERNESTO JORGE PODESTA; ULISES DANIEL ORLANDO

Salta

Congreso; PABMB-SAIB 2019; 2019

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Acil CoA synthetase 4 (ACSL4) is an enzyme which regulates steroidogenesis in physiological conditions. However, in pathological scenarios, an increase in ACSL4 expression is associated to the promotion of a highly aggressive cell phenotype in breast, prostate, colon and liver cancer. ATP-binding cassette (ABC) transporters are transmembrane proteins which use energy through ATP hydrolysis to translocate low-weight molecules. Whereas in physiological conditions these transporters are in charge of maintaining homeostasis in different tissues, for example through steroid efflux, their participation in pathological events is associated to drug resistance, for example through chemotherapeutic drug efflux. Our group has previously reported the involvement of ACSL4 in steroidogenesis and breast cancer chemotherapy resistance, partly mediated by the regulation of the ABCG2 transporter. In this context, and given that adrenocortical cells generate both steroids and highly aggressive tumors such as adrenocortical carcinoma, we used NCI-H295R, a cell line developed from a human adrenocortical tumor, as a steroidogenic and carcinogenic model to study the participation of ACSL4 and ABCG2 in chemotherapeutic drug resistance.