primary cilia and aberrant cell signaling in epithelial ovarian cancer主要在上皮纤毛异常细胞信号传导和卵巢癌.pdfVIP

Egeberg et al. Cilia 2012, 1:15 /content/1/1/15 RESEARCH Open Access Primary cilia and aberrant cell signaling in epithelial ovarian cancer 1,2 1 1 1 1 1 Dorte L Egeberg , Mette Lethan , Robert Manguso , Linda Schneider , Aashir Awan , Tue S Jørgensen , 2 1 1* Anne G Byskov , Lotte B Pedersen and Søren T Christensen Abstract Background: Ovarian cancer is the fourth leading cause of cancer-related deaths among women in Denmark, largely due to the advanced stage at diagnosis in most patients. Approximately 90% of ovarian cancers originate from the single-layered ovarian surface epithelium (OSE). Defects in the primary cilium, a solitary sensory organelle in most cells types including OSE, were recently implicated in tumorigenesis, mainly due to deregulation of ciliary signaling pathways such as Hedgehog (Hh) signaling. However, a possible link between primary cilia and epithelial ovarian cancer has not previously been investigated. Methods: The presence of primary cilia was analyzed in sections of fixed human ovarian tissue as well as in cultures of normal human ovarian surface epithelium (OSE) cells and two human OSE-derived cancer cell lines. We also used immunofluorescence microscopy, western blotting, RT-PCR and siRNA to investigate ciliary signaling pathways in these cells. Results: We show that ovarian cancer cells display significantly reduced numbers of primary cilia. The reduction in ciliation frequency in these cells was not due to a failure to enter growth arrest, and correlated with persistent centrosomal localization of aurora A kinase (AURA). Further, we demonstrate that ovarian cancer cell