Trastuzumab resistance induces EMT to transform HER2(+) PTEN(-) to a triple negative breast cancer that requires unique treatment options.

ABSTRACT: Although trastuzumab is an effective treatment in early stage HER2(+) breast cancer the majority of advanced HER2(+) breast cancers develop trastuzumab resistance, especially in the 40% of breast cancers with loss of PTEN. However, HER2(+) breast cancer patients continue to receive trastuzumab regardless PTEN status and the consequence of therapy in these patients is unknown. We demonstrate that continued use of trastuzumab in HER2(+) cells with loss of PTEN induces the epithelial-mesenchymal transition (EMT) and transform HER2(+) to a triple negative breast cancer. These transformed cells exhibited mesenchymal morphology and gene expression markers, while parent HER2(+) cells showed epithelial morphology and markers. The transformed cells exhibited loss of dependence on ERBB family signal

SUBMITTER: Burnett JP 

PROVIDER: S-EPMC4629137 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature