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

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

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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 Classic Vibrators factor that regulates a 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 knocked out both alleles of the STAT6 gene using somatic cell gene targeting.Interestingly, loss of STAT6 Car Ornament Gift Box 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.