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

Autor: Molly DiScala, Matthew S Najor, Timothy Yung, Deri Morgan, Abde M Abukhdeir, Melody A Cobleigh
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: PLoS ONE, Vol 15, Iss 6, p e0234146 (2020)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0234146
Popis: 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 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 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.
Databáze: Directory of Open Access Journals
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