Epigenetic Silencing of HER2 Expression during Epithelial-Mesenchymal Transition Leads to Trastuzumab Resistance in Breast Cancer.

ABSTRACT: HER2 receptor tyrosine kinase (encoded by the ERBB2 gene) is overexpressed in approximately 25% of all breast cancer tumors (HER2-positive breast cancers). Resistance to HER2-targeting therapies is partially due to the loss of HER2 expression in tumor cells during treatment. However, little is known about the exact mechanism of HER2 downregulation in HER2-positive tumor cells. Here, by analyzing publicly available genomic data we investigate the hypothesis that epithelial-mesenchymal transition (EMT) abrogates HER2 expression by epigenetic silencing of the ERBB2 gene as a mechanism of acquired resistance to HER2-targeted therapies. As result, HER2 expression was found to be positively and negatively correlated with the expression of epithelial and mesenchymal phenotype marker genes, respec

SUBMITTER: Nami B 

PROVIDER: S-EPMC8472246 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature