Study of AKT1, AKT2 and phospho-S6 as potential biomarkers of breast cancer prognosis

PERRONE MARIA CECILIA; RODRIGUEZ MARIA JIMENA; ENRICO DIEGO; LEVY ESTRELLA; BENES MARINA; RIGGIO MARINA; AMAT MORA; NOVARO VIRGINIA; WERBACH ANDREA; GRAÑA KAREN; MANDO PABLO

MAR DEL PLATA

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2019

Sociedad Argentina de Investigación Clínica

PI3K/AKT/mTOR pathway has been shown to be altered in over 70% of breast tumors, and has consequently become a promising therapeutic target. However, PIK3CA and PTEN mutations do not always correlate with pathway activation or breast cancer prognosis. Therefore, there is a need for defining other biomarkers of PI3K/AKT/mTOR activation in order to correctly assess which patients would benefit from using specific inhibitors. We have focused our study on isoforms AKT1 and AKT2 as well as ribosomal protein S6, which have been shown to be upregulated in luminal breast cancer. Previously, in luminal breast cancer cell lines we found that AKT1 promotes cell proliferation through S6 phosphorylation (pS6), while AKT2 favors cell migration and invasion. Moreover, in 46 stage IV luminal breast cancer samples, AKT1 correlates with ki67 staining, whereas AKT2 expression is higher in tumors from patients with earlier relapse. In the present work, we extended our analysis to 62 luminal breast cancer samples (stages I, II and III) in order to further understand the role of PI3K/AKT/mTOR pathway in breast cancer progression. We performed immunohistochemistry for AKT1, AKT2 and pS6 and assessed tumor histology and protein quantification. We found that AKT1 protein levels decrease with greater tumor stage and Nottingham differentiation score (p