Invasive Lobular Carcinoma Cell Lines Are Characterized by Unique Estrogen-Mediated Gene Expression Patterns and Altered Tamoxifen Response

摘要: Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer that frequently associated with favorable outcomes, as ~90% ILC express the estrogen receptor (ER). However, recent retrospective analyses suggest patients receiving adjuvant endocrine therapy may not benefit much invasive ductal carcinoma. Based on these observations, we characterized ER function and response in models. The ER-positive cell lines MDA MB 134VI (MM134) SUM44PE were used to examine ER-regulated transcriptome via gene expression microarray ChIP-Seq, therapy. In parallel, was assessed vivo patient-derived xenograft HCI-013. We identified 915 genes uniquely E2-regulated versus other lines, subset also MM134 cells de novo tamoxifen resistant, induced grow by 4-hydroxytamoxifen, well anti-estrogens, partial agonists. Growth accompanied agonist activity ER-mediated expression. Though growth, required FGFR1 signaling maintain viability sensitive combined inhibition. Our observation drives unique program correlates ability induce growth cells. Targeting factors using inhibitors block survival pathways reverse resistance.