Int J Med Sci 2018; 15(1):46-58. doi:10.7150/ijms.20508
Antioxydation And Cell Migration Genes Are Identified as Potential Therapeutic Targets in Basal-Like and BRCA1 Mutated Breast Cancer Cell Lines
1. Université Clermont Auvergne, Centre Jean Perrin, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, F-63000 Clermont Ferrand, France
2. Département d'Oncogénétique, Centre Jean Perrin, F-63000 Clermont Ferrand, France
3. Biological Resources Center BB-0033-00075, Centre Jean Perrin, F-63000 Clermont Ferrand, France
Privat M, Rudewicz J, Sonnier N, Tamisier C, Ponelle-Chachuat F, Bignon YJ. Antioxydation And Cell Migration Genes Are Identified as Potential Therapeutic Targets in Basal-Like and BRCA1 Mutated Breast Cancer Cell Lines. Int J Med Sci 2018; 15(1):46-58. doi:10.7150/ijms.20508. Available from http://www.medsci.org/v15p0046.htm
Basal-like breast cancers are among the most aggressive cancers and effective targeted therapies are still missing. In order to identify new therapeutic targets, we performed Methyl-Seq and RNA-Seq of 10 breast cancer cell lines with different phenotypes. We confirmed that breast cancer subtypes cluster the RNA-Seq data but not the Methyl-Seq data. Basal-like tumor hypermethylated phenotype was not confirmed in our study but RNA-Seq analysis allowed to identify 77 genes significantly overexpressed in basal-like breast cancer cell lines. Among them, 48 were overexpressed in triple negative breast cancers of TCGA data. Some molecular functions were overrepresented in this candidate gene list. Genes involved in antioxydation, such as SOD1, MGST3 and PRDX or cadherin-binding genes, such as PFN1, ITGB1 and ANXA1, could thus be considered as basal like breast cancer biomarkers. We then sought if these genes were linked to BRCA1, since this gene is often inactivated in basal-like breast cancers. Nine genes were identified overexpressed in both basal-like breast cancer cells and BRCA1 mutated cells. Amongst them, at least 3 genes code for proteins implicated in epithelial cell migration and epithelial to mesenchymal transition (VIM, ITGB1 and RhoA).
Our study provided several potential therapeutic targets for triple negative and BRCA1 mutated breast cancers. It seems that migration and mesenchymal properties acquisition of basal-like breast cancer cells is a key functional pathway in these tumors with a high metastatic potential.
Keywords: Basal-like breast cancer, BRCA1, RNA-Seq, cell migration, antioxydation