Bio-Field Array: The Influence of Junction Mediating and Regulatory Protein Expression on Cytoskeletal Filament Behavior During Apoptosis in Triple-Negative Breast Cancer

Breast Cancer (Auckl). 2019 Feb 28:13:1178223419830981. doi: 10.1177/1178223419830981. eCollection 2019.

Abstract

Introduction: The Bio-Field Array (BFA) is a device that generates a dielectrophoretic electromagnetic field (DEP-EMF) when placed in a hypotonic saline solution and a direct current (dc) of ~3 amperes is applied. Human triple-negative breast cancer (MDA-MB-231 cells) is known to have a high percentage of apoptotic (P53) deficient cells and some patients can have poor outcomes with current treatments.

Objectives: Previously, we reported a strong upregulation of the apoptotic arm of the unfolded protein response, via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as well as positive annexin staining in this human breast carcinoma, when grown in media prepared with BFA's dc DEP-EMF treated saline. Here we will examine and discuss cytoskeletal microtubule changes that were noted in the treated breast carcinoma that are strongly suggestive of apoptosis and the possible correlation of these microtubule changes to the upregulation of Junction Mediating and Regulatory Protein (JMY, a P53/TP53 cofactor) that is known to drive cytoskeleton microfilaments (actin) function.

Methods: In addition to microarray and RT-qPCR analyses, we conducted 7 days of fluorescent microscopic analyses of tubulin assays in these treated versus control MDA-MB-231 cells.

Results: These data suggest 2 possible forms of apoptosis, rounded and irregular, may be occurring and possibly facilitated by the significant upregulation (via microarray and RT-qPCR) of an important but poorly understood Nucleation-Promoting Factor (NPF), JMY.

Conclusions: The ability of the BFA dc DEP-EMF to significantly upregulate JMY and possibly influence the regulation of unbranched (nucleation-microtubule spikes) and branched forms (autophagy) of actin in the cytoplasmic domains may facilitate a "two coffins" or round and irregular necrosis-like apoptosis for this highly aggressive and often apoptotic-deficient breast cancer cell line.

Keywords: JMY; apoptosis; autophagy; cytoskeletal filaments; triple-negative breast cancer.