In search of a molecule responsible of the differential bioelectricity of left/right-sided breast tumors.

GONZALEZ PABLO; MASUELLI S; REAL SEBASTIAN; LAURITO SR; BELLO OSCAR; ROQUE MORENO MARIA

Congreso; REUNION SAIC 2023; 2023

In a serendipitous discovery, our group found epigenetic differences between left and right-sided breast carcinomas (L-R). This unexpected data opened further research that allowed to deepen into the hypothesis that L-R tumors are not identical. Through diverse experimental approaches, we have been able to demonstrate that the epigenetic L-R differences are linked to differences in bioelectrical properties, proliferation rates, composition of stem cells, and patient survival rates. In this study, we aimed to explore an in-vitro approach by conditioning cultured cells with L-R mammary extracts, to evaluate the bioelectrical effect. For this, we used MDA-MB231 cultured cells conditioned with L-R bovine mammary extracts and measured bioelectric states with fluorescent probes (Mitotracker and Dibac) by flow cytometry. We were able to establish that the extracts from bovine mammary gland yielded similar effects as human glandular tissue: cells treated with L extracts exhibit a depolarized membrane potential as compared to the R-treated ones (One sample T-test, p=0,04). Expanding our insights, we separated the extracts in fractions obtained through sequential centrifugations and tested their bioelectrical effects on cells. We saw that the supernatant fraction derived from 50,000rpm centrifugations sustained the distinctive L-R effect of the whole extracts (Unpaired T-test, p=0,004), suggesting the involvement of a small, soluble, low-weight molecule, such as ions or neurotransmitters/hormones. Using a statistical bioinformatic tool R script-based, we conducted Differential Expression Analysis (DEA) on 722 TCGA L-R tumors and found a candidate signature of 7 GABA-related genes (Welch’s t-test, p=0,002). Our findings suggest a potential window for differential treatment between L-R breast tumors, based on the repositioning of druggable ion channels.