Targeting PI3K/AKT pathway to overcome endocrine resistance in breast cancer

MARINA RIGGIO, MARÍA LAURA POLO, MARÍA MAY, CLAUDIA LANARI AND VIRGINIA NOVARO.

Buenos Aires, Argentina

Congreso; Molecular Mechanisms in cell signaling and gene expression, Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular (SAIB); 2013

The phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway is commonly deregulated in tumors that do not respond to antiestrogen therapy, being associated to resistance to endocrine and other therapies. The aim of this study was to target the PI3K/AKT pathway to overcome resistance to endocrine therapy. For this purpose we used the ER-positive IBH-6 human breast cancer cell line. We stably transfected IBH-6 cells to overactivate AKT1 using the myristoylated Akt1 (myrAKT1) construct. While IBH-6 wt cells treated with the antiestrogen ICI182780 (Fulvestrant) decreased cell proliferation, IBH-6-myrAkt1 cells did not. However, the last ones are sensitive to rapamycin. IBH-6-wt and -myrAkt1 cells were inoculated into NOD/SCID mice and tumors were treated for 15 days with ICI, rapamycin, or the combination of both. IBH-6-wt tumors showed no significant changes in tumor growth curves after rapamycin treatment. However, IBH-6-myrAkt1 tumors treated with rapamycin significantly reduced tumor growth (p