Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis

摘要: The Forkhead Box m1 (Foxm1) protein is induced in a majority of human non-small cell lung cancers and its expression associated with poor prognosis. However, specific requirements for the Foxm1 each type cancer lesion remain unknown. present study provides first genetic evidence that respiratory epithelial cells essential tumorigenesis. Using transgenic mice, we demonstrated conditional deletion from (epFoxm1(-/-) mice) prior to tumor initiation caused striking reduction number size tumors, by either urethane or 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT). Decreased tumorigenesis epFoxm1(-/-) mice was diminished proliferation reduced Topoisomerase-2alpha (TOPO-2alpha), critical regulator proliferation. Depletion mRNA cultured adenocarcinoma significantly decreased TOPO-2alpha levels. Moreover, directly bound transcription mouse promoter region, indicating direct target cells. Finally, pre-existing tumors dramatically growth lung. Expression formation vivo, suggesting promising anti-tumor therapy.