E2F1 AND RB ARE COMMON MEDIATORS OF THE INHIBITORY EFFECTS PROMPTED BY THE COMBINATION OF MIFEPRISTONE AND PALBOCICLIB ON BREAST CANCER CELLS EXPRESSING PROGESTERONE RECEPTOR ISOFORM A

PATACCINI, GABRIELA; LANARI, CLAUDIA; GIULIANELLI, SEBASTIÁN

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

SAIC SAI&FAIC SAFIS

Palbociclib (PALBO), a CDK 4/6 inhibitor, is currently used in combinationwith endocrine therapy targeting estrogen receptors to treatadvanced luminal breast cancer. However, with time tumors becomeresistant to these treatments highlighting the need to develop othertherapeutic strategies. Our laboratory focuses on the use of therapiestargeting progesterone receptors (PR). We have previouslyshown that PALBO inhibits luminal breast cancer cell proliferationregardless of the prevailing PR isoform expressed and that mifepristone(MFP), an antiprogestin, potentiates this effect only in cells expressingPR isoform A (PRA). The aim of this study was to evaluatethe role of two key cell cycle proteins, RB and E2F1 as mediatorsof this effect. T47D-YA or T47D-YB cells, expressing respectivelyPRA or PRB were treated with MFP, PALBO, or MFP+PALBO. Theexpression of E2F1 and pRB was evaluated by western blots. Inagreement with data obtained in cell proliferation studies, a significantdecrease of both protein levels (p