Role of PI3K/AKT/mTOR pathway in Tamoxifen and Palbociclib resistance in breast cancer

RODRIGUEZ MARÍA JIMENA, PERRONE MARÍA CECILIA, RIGGIO MARINA, BENES MARINA, ALCOBER BOQUET LUCÍA, NOVARO VIRGINIA.

Bariloche

Simposio; The Fourth South American Spring Symposium in Signal Transduction and Molecular Medicine? (SISTAM 2018) Bariloche, Argentina; 2018

Role of PI3K/AKT/mTOR pathway in Tamoxifen and Palbociclib resistance in breast cancerRodriguez María Jimena, Perrone María Cecilia, Riggio Marina, Marks Paula, Benes Marina, Alcober Boquet Lucía, Novaro VirginiaInstituto de Biología y Medicina Experimental (IBYME-CONICET)jimena.rod01@gmail.comApproximately 70% of breast tumors express estrogen (ER) and progesterone (PR) receptors. Although the ER antagonist Tamoxifen has been successful for ER+ breast cancer treatment, a significant amount of these tumors eventually develop resistance. In this context, Palbociclib (a CDK4/6 inhibitor) has recently been approved for the treatment of breast tumors which relapse after hormone therapy. The aim of this work was to generate Tamoxifen- and Palbociclib-resistant cell lines in order to study mechanisms of acquired resistance. We used the T47D cell line to generate resistant lines by long-term exposure to progressively increasing concentrations of Tamoxifen (T47D-TR), Palbociclib (T47D-PR) and Tamoxifen+Palbociclib (T47D-TPR) to mimic what occurs in the clinic.All resistant cell lines showed decreased levels of ER and PR (p