Project name: RNA sequence analysis of stable versus reversible EMT events and the resultant metastases

Description: The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states is critical to complete the metastatic process. In contrast, induction of epithelial-mesenchymal transition (EMT) through the acquisition of drug persistence is a more stable event. Herein, we utilize Her2 transformed human mammary epithelial (HMLE) cells to compare a reversible model of EMT induced by TGF-beta to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor, lapatinib. Indeed, only a TGF-beta cells capable of returning to an epithelial phenotype resulted in long bone metastasis (BM). These four cell populations were anylzed by RNA sequencing.Overall design: The Her2 transformed HMLE cells are referred to as the parental (Par) cell line and serves as the control. These cells were treated with TGF-beta every three days for a period of 4 weeks to induce EMT (TGFB). Alternatively, the parental cells were treated with 1 micromolar of lapatinib every three days also for 4 weeks and a proliferative drug resistant population (LAPR) emerged. The TGF-beta treated cells were engrafted onto the mammary fatpad and resultant long bone metasases (BM) were isolated and subcluted ex-vivo.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Last updated: 2018-06-03