Dielectrophoretic properties distinguish responses to estrogen and fulvestrant in breast cancer cells

Abstract

The majority of breast tumors express estrogen receptors (ER), and are treated with endocrine therapy (ET) drugs to target ERs and estrogen (E2) biosynthesis in the management of early and metastatic ER + breast cancer. However, ∼50% of patients receiving an ET exhibit either intrinsic (de novo) resistance or acquire resistance to these treatments despite persistent expression of ER in the tumors. Thus, an assay to better predict the drug responsiveness of ER targeting ET drugs, such as fulvestrant (Ful) would be beneficial for clinical treatments. Here, we compared two genetically related cell lines isolated from ER+ MCF-7 human breast cells: the LCC1 (Ful-sensitive (s)) and LCC9 Ful-resistant (r)). Using passivated-electrode insulator-based dielectrophoresis (π DEP), the DEP profile of LCC1 and LCC9 Ful-response were compared. Ful-s LCC1 cells responded with a gradual crossover frequency (f0) shift from 700 kHz to 300 kHz over 72 h. The Ful-r LCC9 cells showed a gradual f0 shift from 100 kHz to 700 kHz over this time period. In response to E2, LCC1 cells showed a small f0 shift from 700 kHz to 600 kHz while LCC9 showed a large f0 change from 100 kHz to 800 kHz. There are no significant differences in gene pathway-specific mRNA expression between the LCC1 and LCC9 cells. Nevertheless, several mRNAs identified in an unbiased screen are differentially expressed in LCC1 and LCC9 cells including PALLD, ADAP1, SLC12A2, and TM4SF1. Investigation of these genes could begin to clarify how responses to ET translate into changes in cellular bioelectric properties and contribute to validation of DEP ET response biomarkers.