2026-07-21T14:41:54Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/235612024-11-29T03:08:32Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Sofia, Masuelli author Sebastian, Real author Emanuel, Campoy author Branham, Maria Teresita author Matias Marzese, Diego author Matthew, Salomon author De Blas, Gerardo author Rodolfo, Arias author Michael, Levin author Maria, Roque author 2022-12 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. Sofia M, Sebastian R, Emanuel C, Branham MT, Marzese DM, Matthew S, et al. When left does not seem right: epigenetic and bioelectric differences between left- and right-sided breast cancer. Mol Med. 2022 Dec;28(1):15. 10.1186/s10020-022-00440-5 1528-3658 1076-1551 Molecular Medicine https://hdl.handle.net/20.500.13003/19912 35123413 L2014948285 2-s2.0-85124232371 https://hdl.handle.net/20.500.12105/23561 751622300004 Asymmetry Laterality Left Right Breast cancer When left does not seem right: epigenetic and bioelectric differences between left- and right-sided breast cancer