DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer

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Abstract

Background Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood. Methods Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis-specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group). Results Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P

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Woditschka, S., Evans, L., Duchnowska, R., Reed, L. T., Palmieri, D., Qian, Y., … Steeg, P. S. (2014). DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer. Journal of the National Cancer Institute, 106(7). https://doi.org/10.1093/jnci/dju145

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