A novel interaction between HER2/neu and cyclin E in breast cancer

摘要: HER2/neu (HER2) and cyclin E are important prognostic indicators in breast cancer. As both involved cell cycle regulation we analyzed whether there was a direct interaction between the two. HER2 expression levels were determined 395 cancer patients. Patients with HER2-overexpression high of had decreased 5-year disease-specific survival compared low (14% versus 89%, P<0.0001). In vitro studies performed which HER2-mediated activity HER2-overexpressing lines downregulated by transfection small interfering RNA or treatment trastuzumab. Cyclin western blot analysis, functional effects using kinase assays, MTT assays used to assess viability as marker proliferation fluorescence-activated sorting analysis determine profiles. Decreased signaling resulted E, particularly molecular weight (LMW) isoforms. LMW consequences, including E-associated proliferation, because increased apoptosis an accumulation cells G1 phase. vivo xenograft model confirmed trastuzumab on expression. Given relationship clonogenic combination therapy targeting proteins. Isobologram showed synergistic two agents (trastuzumab roscovitine E). Taken together, these show that expression, turn deregulates cycle. has predictive roles cancer, warranting further study its potential therapeutic target.