14-3-3 σ Expression Effects G2M Response to Oxygen and Correlates with Ovarian Cancer Metastasis 英文参考文献.docVIP

14-3-3sExpressionEffectsG2/MResponsetoOxygen andCorrelateswithOvarianCancerMetastasis DashnamoorthyRavi1,2,YidongChen1,3,,BijalKaria1,2,AdamBrown1,2,TingTingGu1,JieLi4,MarkS. Carey4,5,BryanT.Hennessy4,6,AlexanderJ.R.Bishop1,2 * 1GreeheyChildren’sCancerResearchInstitute,UniversityofTexasHealthScienceCenter,SanAntonio,Texas,UnitedStatesofAmerica,2DepartmentofCellularand StructuralBiology,UniversityofTexasHealthScienceCenter,SanAntonio,Texas,UnitedStatesofAmerica,3DepartmentofEpidemiologyandBiostatistics,Universityof TexasHealthScienceCenter,SanAntonio,Texas,UnitedStatesofAmerica,4DepartmentofGynecologicMedicalOncology,UniversityofTexasMDAndersonCancer Center, Houston, Texas, United States of America, 5Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver,Canada,6DepartmentofMedicalOncology,BeaumontHospital,Dublin,Ireland Abstract Background: In vitro cell culture experiments with primary cells have reported that cell proliferation is retarded in the presence of ambient compared to physiological O2 levels. Cancer is primarily a disease of aberrant cell proliferation, therefore,studyingcancercellsgrownunderambientO2maybeundesirable.TounderstandbettertheimpactofO2onthe propagationofcancercellsinvitro,wecomparedthegrowthpotentialofapanelofovariancancercelllinesunderambient (21%)orphysiological(3%)O2. Principal Findings: Our observations demonstrate that similar to primary cells, many cancer cells maintain an inherent sensitivity to O2, but some display insensitivity to changes in O2 concentration. Further analysis revealed an association between defective G2/M cell cycle transition regulation and O2 insensitivity resultant from overexpression of 14-3-3 s. Targeting 14-3-3 s overexpression with RNAi restored O2 sensitivity in these cell lines. Additionally, we found that metastaticovariantumorsfrequentlyoverexpress14-3-3s,whichinconjunctionwithphosphorylatedRB,resultsinpoor prognosis. Conclusions:Cancercellss