Electrochemical assay of the relationship between the inhibition of phosphatidylinositol 3-kinase pathway and estrogen receptor expression in breast cancer

Breast cancer has become one of the most threatening diseases to women throughout the world. Emerging evidence implies that estrogen receptor (ER) and phosphatidylinositol 3-kinase (PI3K) pathways play central roles in both breast cancer progression and response to therapy. In this work, we have probed into ER expression related to the PI3K pathway at the protein level with an electrochemical technique based on the detection of ER proteins in nuclear extracts with an Exonuclease III protection-based strategy. Experimental results show that an increased number of ER proteins can be detected upon PI3K inhibition, demonstrating the reversal effect of the PI3K inhibitor on ER expression. Moreover, treatment with different concentrations of the PI3K inhibitor NVP-BEZ235 can result in a dose-dependent alteration of ER protein levels, implying an intimate link between ER and PI3K pathways. This work may be a great help to understand the mysteries underlying PI3K-related endocrine resistance and to evaluate the effect of therapeutic interventions in the future.