Epidermal growth factor-receptor activation modulates Src-dependent resistance to lapatinib in breast cancer models.

ABSTRACT:

Introduction

Src tyrosine kinase overactivation has been correlated with a poor response to human epidermal growth factor receptor 2 (HER2) inhibitors in breast cancer. To identify the mechanism by which Src overexpression sustains this resistance, we tested a panel of breast cancer cell lines either sensitive or resistant to lapatinib.

Methods

To determine the role of Src in lapatinib resistance, we evaluated the effects of Src inhibition/silencing in vitro on survival, migration, and invasion of lapatinib-resistant cells. In vivo experiments were performed in JIMT-1 lapatinib-resistant cells orthotopically implanted in nude mice. We used artificial metastasis assays to evaluate the effect of Src inhibition on the invasiveness of lapatinib-resistant cells. Src-dependent sig

SUBMITTER: Formisano L 

PROVIDER: S-EPMC4076622 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature