The Expression Of FOXM1 In Lung Cancer And Its Carcinogenic Molecular Mechanism

Objectives:To explore the potential effect of FOXM1 expression on the prognosis of lung cancer, we employed FOXM1 promoter report assay and also investigated the expression of FOXM1 in different cell lines and its possible carcinogenic mechanism.Methods:1. The target promoter gene was obtained by PCR and then was connected with empty reporter assay carrier.2. The expression of FOXM1 and KI-67 in 80 lung cancer tissues was analyzed by immunohistochemical methods. The base data of clinical cases were collected and the relationship between the two indexes and survival time was analyzed.3. The possible effect of gefitinib on FOXM1 expression was detected by immunofluorescence.4. The expression of FOXM1 in different cell lines was determined by Western blot, real-time PCR and transfection.5. The impact of nicotine on FOXM1 was studied by detecting the fluorescence intensity of reporter assay.6. To evaluated the effects of oncogene or tumor suppressor gene on FOXM1 expression, selected genes (c-myc,β-catenin, AKT, RasN17, EP300) was cotransfected with FOXM1 respectively by reporter gene assay.Results:1. The strong staining rate of KI-67 was 61.25%, moderate staining rate was 26.25%, and negative staining rate was 12.50% in 80 cases of carcinoma. The strong staining rate of FOXM1 was 66.25%, moderate staining rate was 25.00%, and negative staining rate was 8.75%. The expression of KI-67 and FOXM1 was positive correlation(r=0.437). In non-smoking group, the survival time of cases which FOXM1 low expression group is longer than the higher expression group,χ2=4.439, P=0.035. In smoking group, the survival time of FOXM1 low expression group is shorter than the higher expression group, x2=4.613, P=0.032. 2. The fluorescence intensity of nicotine group was stronger than that of control group.3. The FOXM1 expression in lung cancer cell lines was also detected by Real-time PCR, Western blot and transfection.4. The expression of FOXM1 and CCNB1 showed an abnormal ratio in PC9/AB2 cell lines.5. The fluorescence intensity of cells in gefitinib group was weaker than that of control group.6. The fluorescence intensity of cells in Cotransfection group was stronger than that of control group, however the fluorescence intensity of cells in tumor suppressor gene group is weaker than that of control group.Conclusions:1. FOXM1 has higher expression in lung cancer tissues and was also associated with poor prognosis.2. Nicotine can up-regulate the expression of FOXM1 in cell lines and Gefitinib can down-regulate the expression of FOXM1, which may be possible mechanisms of tumor pathogen. Oncogene c-myc-,β-catenin,AKT can upregulate FOXM1 expression, tumor suppressor gene RasN17, EP300 can downregulate FOXM1 expression in lung cancer cell lines.3. The abnormal expression of FOXM1 and CCNB1 may be related to PC9/AB2 cellular resistance mechanisms.