Approximately 20% of breast cancers are HER2-positive.Trastuzumab has improved patient outcomes significantly for these cancers.However, acquired resistance remains a major hurdle in the clinical management of these patients.Therefore, identifying molecular changes that cause trastuzumab resistance is worthwhile.STAT6 is a transcription factor that regulates a grand love red heart reposado tequila variety of genes involved in cell cycle regulation, growth inhibition, and apoptosis.
STAT6 expression is lost in approximately 3% of breast cancers, but little work has been done in the context of trastuzumab resistance in breast cancer.In isogenic cell line pairs, we observed that trastuzumab-resistant cells expressed significantly lower levels of STAT6 compared to trastuzumab-sensitive cells.Therefore, in order to study the consequences of STAT6 loss in HER2+ breast cancer, we jerome brown jersey knocked out both alleles of the STAT6 gene using somatic cell gene targeting.Interestingly, loss of STAT6 resulted in anchorage-independent growth and changes in several genes involved in epithelial to mesenchymal transition.This study suggests that STAT6 may play a role in the pathophysiology of HER2+ human breast cancer.