changes in gene expression and cellular architecture in an ovarian cancer progression model基因表达和细胞结构的变化在一个卵巢癌发展模型.pdfVIP

Changes in Gene Expression and Cellular Architecture in an Ovarian Cancer Progression Model 1 2 2 2 3 Amy L. Creekmore , William T. Silkworth , Daniela Cimini , Roderick V. Jensen , Paul C. Roberts *, Eva M. Schmelz1* 1 Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 2 Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America, 3 Department of Biomedical Science and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America Abstract Background: Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. Methodology/Principal Findings: Mouse ovarian surface epithelial (MOSE) cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non- tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cyt