ACYL-COA SYNTHETASE-4, A NEW POTENTIAL THERAPEUTIC TARGET IN HORMONE-RESISTANT BREAST CANCER

CASTILLO ANA FERNANADA; ORLANDO ULISES; DATTILO MELINA; MALOBERTI PAULA; SOLANO ANGELA; PODESTA ERNESTO JORGE

Mar del Plata,

Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

Acyl-CoA synthetase 4 (ACSL4) expression, an enzyme working in arachidonic acid metabolism, has beenassociated with breast carcinoma. The triple-negative tumor (TN) is a subtype of breast cancer that exhibits poorprognosis and no effective therapy is readily available. Therefore, the identification of new therapeutic targets iscritical to improve the management of a significant proportion of cancer patients. We show that knocking downACSL4 expression in TN cell line, MDA-MB-231, induces estrogen receptor (ERα) expression. ACSL4overexpression decreases the level of ERα. By means of the MCF-7 Tet-Off/ACSL4 model system, which involves areduction in ERα levels, we used a pharmacological approach to inhibit cell proliferation through a combination ofsub-maximal doses of tamoxifen and rosiglitazone, an ACSL4 inhibitor. Drugs alone did not produce a significantinhibition in cell proliferation. However, the combination of the two inhibitors was much more efficient, showing aremarkable synergistic effect. ERα and ribosomal p-S6 protein levels were monitored to confirm that rosiglitazonetreatment indeed increased ERα expression and decreased the mTOR signal. The presence of ACSL4 could be aprognostic factor for hormone resistance in ERα-positive breast cancer tissues. A combined therapy could thus bevery useful in actually preventing the appearance of hormone resistance.