Loss of STAT6 leads to anchorage-independent growth and trastuzumab resistance in HER2+ breast cancer cells.

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. is a transcription factor that regulates a variety of genes involved in cell cycle regulation, growth inhibition, and apoptosis. duanyu18136 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 duanyu18136 compared to trastuzumab-sensitive cells. Therefore, in order to study the consequences of duanyu18136 loss in HER2+ breast cancer, we knocked out both alleles of the duanyu18136 gene using somatic cell gene targeting. Interestingly, loss of duanyu18136 resulted in anchorage-independent growth and changes in several genes involved in epithelial to mesenchymal transition. This study suggests that duanyu18136 may play a role in the pathophysiology of HER2+ human breast cancer.

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