Abstract 3458: Role of the EphB1 gene in mediating migration, proliferation, and radiosensitization of medulloblastoma cells

Eph/ephrin signaling in a variety of cancers has been reported to promote aspects of tumorigenesis, including proliferation, migration, and angiogenesis. Medulloblastoma is an aggressive primitive neuroectodermal tumor originating in the cerebellum. Recently performed integrative genomic approach to a large cohort of medulloblastomas has identified four subtypes (A-D) based on clinical presentation, transcription profiles, genetic abnormalities, and clinical outcome. We show high levels of EphB1 expression in tumors derived from children with group D medulloblastomas, which are known to exhibit a poorer response to current therapies. The purpose of this study is to examine the effect knockdown of EphB1 has on cellular migration, proliferation, and radiosensitization of medulloblastoma tumors. Using a human-derived medulloblastoma cell line (DAOY) and small interfering RNA (siRNA) targeting EphB1, we compared cell migration in an electrical impedance-based transwell Boyden chamber assay (xCELLigence RTCA DP system). We show that siRNA knockdown of EphB1 results in significantly decreased migration. Assessment of proliferation by MTT assay indicates that knockdown of EphB1 affects cell cycle progression in DAOY. Results from cell cycle and sub-G1 analysis by flow cytometry demonstrate that knockdown of EphB1 results in G1 arrest. Our previous systems analysis investigation of global gene expression regulated by an intact ATM gene product also identified EphB1 as a downstream si...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research