Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells

摘要: Development of endocrine resistance during tumor progression represents a major challenge in the management estrogen receptor alpha (ERα) positive breast tumors and is an area under intense investigation. Although underlying mechanisms are still poorly understood, many studies point towards ‘cross-talk’ between ERα MAPK signaling pathways as key oncogenic axis responsible for development estrogen-independent growth cancer cells that initially ERα+ hormone sensitive. In this study we employed metastatic xenograft model harboring constitutive activation Raf-1 to investigate mechanistic linkage aberrant activity through abrogation axis. We demonstrate first time causal role Aurora-A mitotic kinase SMAD5 nuclear down-regulation expression cells. This contribution highly significant treatment refractory carcinomas, because it may lead novel molecular therapies targeting Aurora-A/SMAD5 postulate such therapy result selective eradication resistant ERαlow/− from bulk with consequent benefits patients.