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Mol Med ; 28(1): 15, 2022 02 05.
Article in English | MEDLINE | ID: mdl-35123413

ABSTRACT

BACKGROUND: During embryogenesis lateral symmetry is broken, giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. METHODS: We performed in-silico analyses on breast tumors of public datasets, developed xenografted tumors, and conditioned MDA-MB-231 cells with L/R mammary extracts. RESULTS: We found L/R differential DNA methylation involved in embryogenic and neuron-like functions. Focusing on ion-channels, we discovered significant L/R epigenetic and bioelectric differences. Specifically, L-sided cells presented increased methylation of hyperpolarizing ion channel genes and increased Ca2+ concentration and depolarized membrane potential, compared to R-ones. Functional consequences were associated with increased proliferation in left tumors, assessed by KI67 expression and mitotic count. CONCLUSIONS: Our findings reveal considerable L/R asymmetry in cancer processes, and suggest specific L/R epigenetic and bioelectric differences as future targets for cancer therapeutic approaches in the breast and many other paired organs.


Subject(s)
Electric Impedance , Epigenesis, Genetic , Unilateral Breast Neoplasms/genetics , Unilateral Breast Neoplasms/pathology , Animals , Cell Line, Tumor , Computational Biology , DNA Methylation , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Transcriptome , Tumor Microenvironment
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