Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib

摘要: Background Basal-like and triple negative breast cancer (TNBC) share common molecular features, poor prognosis a propensity for metastasis to the brain. Amplification of epidermal growth factor receptor (EGFR) occurs in ~50% basal-like cancer, mutations have been reported up ~ 10% Asian TNBC patients. In non-small cell lung several different EGFR tyrosine kinase domain confer sensitivity inhibitors, but tumourigenic potential cells their targeted therapy is unknown. Materials Methods Constructs containing wild type, G719S or E746-A750 deletion mutant forms were transfected into MCF10A tumorigenic derivative, MCF10CA1a. The effects over-expression mutation on proliferation, migration, invasion, response gefitinib, tumour formation vivo was investigated. Copy number analysis whole exome sequencing MCF10CA1a lines also performed. Results Mutant increased proliferation gefitinib sensitivity. EGFR-E746-A750 migration greatly xenograft growth. Compared cells, exhibited large regions gain chromosomes 3 9, chromosome 7, many genes implicated cancer. Conclusions enhances oncogenic properties line, increases gefitinib. Although addition renders more it not accompanied by sensitivity, perhaps due additional mutations, including PIK3CA H1047R mutation, that line has acquired. Screening TNBC/basal-like may prove useful directing but, as accompanying resistance.