Research Of EGFR/PTEN Expression And Related Apoptosis And Invasion By In Human Glioma

Gliomas are the most common malignant disease,over the past years,even though on the up in clinical glioma has been a series of active treatment measures,but the plastic stromal tumors in patients with the mortality rate remains high,so gliomas are still the refractory disease in field of neurosurgery,the study of its etiology, pathogenesis,biology characteristics as well as new means of effective treatment has become a hot topic in neurosurgery.Much current research has confirmed that the incidence of tumor development is a gene involved in steps in the evolution of complex process.Therefore,glioma is essentially a multi-gene disorders,which are happened because of the activation of oncogenes and tumor suppressor inactivation of genes cause cell cycle through the line changes.The abnormal signal transduction pathways,the life-cycle extension,as well as defects in apoptosis and so on,and thus give rise to out-of-control cell proliferation and malignant transformation.With the medical technology of molecular biology,the gene therapy of glioma study has been made exciting progress,and has the transition to clinical research stage.However,in glioma gene therapy of animal experiments and clinical studies will still encounter problems relating to the validity of questions,such as how to effectively impede the gene therapy to overcome some barriers and exert the greatest extent possible gene therapy treatment of the role of biology became a major research topic.Some protein growth factors and their receptors have been identified as protp-oncogene.Epidermal growth factor and its receptor have been most concerned. Human EGFR gene located in chromosome 7p11-13,and many of tumor cells have over-expression of EGFR.EGFR is a proto-oncogene c-erB-1(HER-1)expression of the product,encoded by anâ… -type transmembrane protein tyrosine kinase growth factor receptor,the molecular weight of about 170kD generally expressed in human epidermal cells and stromal cells,the conversion information in the membrane play an important role,and is highly expressed in a variety of human malignancies.Signal transduction of it mediated have many effects,including proliferation,migration,cell differentiation and the stability of the environment,and is closely related to cell regeneration and the occurrence,development of malignant tumors.PTEN gene has been cloned is the first of a phosphatase activity of tumor suppressor genes,play a important role in regulating cell growth and apoptosis,cell signal transduction and tumor cell invasion,metastasis,etc.At present,we consider the role of PTEN tumor suppressor is a few ways to achieve the adoption as following: (1)Inhibited cell movement and infiltration through the phosphorylation of FAK.(2) Prevent cell growth and promote apoptosis by PIP3 dephosphorylated.(3)Inhibits cell growth and differentiation by inhibited cell MAPK signal transduction pathway.In recent years,tissue microarray developed as a morphology-based molecular biology techniques.It can be sliced up on a high-throughput access to histology,gene and protein expression information.It can simultaneously detect a tumor gene expression at different stages of the situation at the same time.It is also low cost,easy to operate.Application of tissue microarray can be used for gene expression detection, diagnosis and treatment to verify the specificity of target gene expression,detection and optimization of probes and antibodies,drug screening and disease diagnosis and so on.ObjectiveTo explore EGFR,PTEN,MMP-2/9,Caspase-9 and Bcl-2 expression in human gliomas and its relation with the degree of glioma maligancy.MethodsIn order to further elucidate human glioma EGFR and PTEN gene in the regulation of glioma proliferation and invasive growth and downstream gene expression,the subject of the application of tissue microarray analysis of 60 cases of glioma specimens have been detected.Further application of immunohistochemical method in the analysis of the expression level of EGFR,PTEN,MMP-2 / 9, Caspase-9 and Bcl-2 and the correlation between the degree of malignant glioma the contact have been made.ResultsThe expression of EGFR,MMP-2,MMP-9,BCL-2 is the plasma-positive.And different levels of expression between glioma have differences.With the increased level of its expression positive rate and the degree of expression was followed by increases.Expression levels of the EGFR signaling pathway glioma important members such as EGFR,MMP-2,MMP-9,BCL-2 by immunohistochemical analysis showed that:the above indicators at glioma positive rate and expression level of tumor with the degree of malignancy increases at low level and between malignant glioma significant statistical difference.Expression of PTEN and Caspase-9 at different levels between glioma also vary,but with the increased level of its expression positive rate and expression of positive degree is followed by reduced. Immunohistochemical analysis also showed:PTEN and Caspase-9 in glioma positive rate and expression level increased with the degree of malignant tumor is reduced,at low level and between malignant glioma significant statistical difference. Correlation analysis also found that EGFR,PTEN,MMP-2,MMP-9,Caspase-9, BCL-2 exists between the relationship significant.EGFR,PTEN,MMP-2/9, Caspase-9 and Bcl-2 between these factors and related statistically significant.Conclusion:That indicating that each of these indicators probably exist the interaction or synergy,but also implies that the above-mentioned factors have important effect in the malignant glioma.EGFR and PTEN gene has played an important role in the occurrence and development of glioma,can be used as a candidate gene for gene therapy.