| At present,lung cancer has become the most common malignant tumor,each year nearly 1.2 million cases of new cases,but also the main cause of cancer death in men.The activating transcription factor 2(ATF2),is a member of the c AMP response element binding(CREB)family which is an important element of transcription complex.ATF2 elicits both oncogenic and tumor suppressor activities depending its different positioning in cell nucleus and cytoplasm.ATF2 acts as a cancerogenic factor when it locates in cell nucleus and acts as a cancer suppressor factor when it in cytoplasm.The present study was aimed at discussing the relationship between ATF2 and lung cancer malignant behavior and its clinical significance.And we investigated the expression of ATF2 in non-small cell lung cancer cell line,to determine ATF2 as a biomarker of non-microcystic pulmonary carcinoma prognosis.Objective: To investigate the effect of ATF-2 protein expression on the proliferation and prognosis of non-small cell lung cancer(NSCLC)cells.Methods: In this study,reverse transcriptase quantitative polymerase chain reaction and Western-blot were used to detect the ATF2 expression in fresh NSCLC tumors and its adjacent tissues,and we analyzed the correlation of ATF2 and cell proliferation,invasion and metastasis and poor prognosis.We used quantitative real-time-PCR to detect the mRNA of ATF2 in fresh NSCLC tumors before and after transfection(48h).The expression and cellular localization of immunohistochemistry.ATF2 protein in non small cell lung cancer by immunohistochemical NSCLC expression and cellular localization of ATF2 protein determination method.To construct the eukaryotic expression vector of ATF2,because the ATF2 expression in HBE cells,and to study the effects of increased ATF2 expression,by WST-8 method and colony growth and proliferation of formation experiments cells.Detection of ATF2 binding domain(HBD)effect,through the WST-8 test of H520 cells,and the analysis of the action of of HBD on the growth of lung cancer cells.In addition,iron pool HBE cell ATF2 expression increased instability in the H520 cells and ATF2 expression decreased fluorescence measurement.Results: We found that the levels of mRNA of ATF2 were markedly increased in NSCLC fresh cancer tissues,and the ATF2 were overexpressed in both NSCLC cell lines and fresh cancer tissues.The expression of ATF2 had correlation with clinical stages.The expression of ATF2 and p-ATF2 had no significance correlation with the age,gender and tumor sizes(P>0.05).Furthermore,NSCLC patients with high ATF2 expression survived shorter than those with low ATF2 expression.Immunohistochemistry data also revealed that the expression of p-ATF2 was mainly in cell nucleus.Among 86 fresh cancer tissues,there were 65 cases high expression(75.6%).There were no significant difference between cell nucleus and cytoplasm of the expression of ATF2.No significant difference were detected in para-carcinoma tissue between ATF2 and p-ATF2(P=0.056).The expression of ATF2 was positive in NSCLC cell lines,and the levels of expression of ATF2 in H446、H1975、H1650,H1299,PC9 were significantly higher.In addition,when knockdown ATF2 expression using RNAi and MTT technic,we found cells copy number decreased which may indicated that ATF2 could suppress cell proliferation.In HBE cell line,the over-expression of ATF2 could promote cell proliferation.Conclusion: Our study demonstrated that ATF2 was remarkably overexpressed in NSCLC and could be served as a potential prognostic marker for patients with this deadly disease.In vitro studies have shown that ATF2 can promote the proliferation of lung cancer cells.Describes the mechanism of the proliferation and growth of lung cancer cells.This study suggests that,ATF2 could be a novel target of tumor treatment,and may suggest the ideas and basis of treatment of malignant tumors.Moreover,ATF2 is expected to become a new molecular drug for the treatment of malignant tumors. |
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