The Expression Of Cx43 Gene And Their Relationship With Cellular Proliferating Activity In Human Brain Glioma

Objective: Intracranial tumors account for 2% of the whole systemic tumors. The annual incidence of intracranial tumor is 1/10000 in which Glioma is the most common malignant tumor, In the later years, surgery, radiotherapy and chemotherapy have been widely applied in treating the patients who sufferring from glioma, which have relieved the patients in some degree. But which is disappointed the relapse ratio is high and the prognosis hasn't improved. The main cause lies in that the biological behavior is complex and the little knowlage of the clinic neuro-surgery about it. Which is the main problems of study in glioma.With the significant advances of molecular biology,it has been demonstrated that the development of malignant tumors, including gliomas, is due to the activation of protooncogenes and inactivation of tumor suppressor genes. Recent studies indicate that reduced expression of Connexin(Cx) genes and downregulated Gap junction intercellular communication(GJIC) have been observed in numerous cancer cells. So Cx genes and GJIC may play an important role in the malignant progression in gliomas. Connexin (Cx),the gap junction protein, is encoded by a family of genes with 13 members. Because of the specificity of Cx gene expression in various tissues, the major Cx gene expressed in adult normal brain tissues are Cx43 and Cx32 genes. The Cx43 gene expression is mainly in astrocytes, while the Cx32 gene expression in oligodendroglioma and some neurons. Up to date, there have been some reports on the expression of Cx43 genes in gliomas, but these results were obtained from a small number of brain tumors or glioma cell lines. The relationship among Cx43 genes expression, histopathological type, proliferation activity and the biological behavior of gliomas has not been reported.In recent years, proliferative cell nuclear antigen (PCNA), a kind of cell period regulating protein, is knew as important index to observe cell proliferative activity. The synthesis level of PCNA indicates cell proliferative rate and DNA synthesis rate.. So PCNA is a valid multiplication period marker in recent research on neoplasm multiplicative action.In this experiment,we make a analysis of the relationship between the expression of CX43 and the hyperplasy of gliomas by to detecting the expression of CX43 and protein with PCNA as an index of cell multiplication and then to investigate the expression's effect on the development. It could offer some objective evidences to study the degree of glioma, the treatment after surgery and the overview of curative effect. Material and method: All the 47 observation cases came from the wax—encapsulated tissue specimens in file of the hospitalized patients all which a pathological as of primarily glioma by pathological diagnosis after surgery. We also had 10 cases of normal brain tissue specimens as control. (all from internal decompression). The technique of immunohistochemistry and in situ hybridization were used to detect the expression of CX43, PCNA were detected by the technique of SP immunohistochemistry.Result:1 The positive expression rates of cx43mRNA are 100% in normal brain tissue and 61.7% in glioma tissue which shows the deviation between experiment group and control group(P<0.01).In olig-malignant glioma tissue(I/II),the expression rates of Cx43 are 100.0% and 93.8% ,compared with the 33.3% and 16.7% in hypsi-malignant glioma tissue(III/IV). The conclusion can be drawed that the relashionship of the expression rate and the grade of glioma is negative correlation, and there is deviation between olig-malignant tumor and hypsi-malignant tumor(P<0. 05).2 The expression of Cx43 proteinum is similar to Cx43mRNA in normal brain tissue and glioma of different grades .There is statistical significance (P<0.01)between experiment group and control, which indicating that with the advance of the histology of glioma the expression of Cx43 proteinum shows decrease tendency(P<0.05). 3 In normal brain tissue, the expression of PCNA is all negative, compared with the positive expression rate of 76.6% in glioma tissue. (P<0.01) In different grades of glioma the expression order is 100.0% in gradeⅣ, 94.4% in grade III, 62.5% in grade II and 42.9% in grade I. The expression rate of PCNA and the grades of glioma are positive correlation(P<0.05), and there are obvious difference between grade III/ IV and I/II.4 The expression of Cx43mRNA, Cx43 proteinum and PCNA in glioma shows that there is significant positive correlation between the expression result of Cx43 and Cx43mRNA(P<0.01 ). With the falling-off of Cx43mRNA and the proteinum, PCNA shows the raising tendency. Statistical analysis shows the negative correlation between the expression of Cx43mRNA, Cx43 proteinum and PCNA in glioma(P<0.05).Conclusion:1 The expression of Cx43mRNA in glioma is negatively related with grade of glioma.The more malignant of glioma,the lower expression of Cx43mRNA,even none expression.2 The expression of Cx43 proten in glioma is negatively related with grade of glioma.And it is positively related with The expression of Cx43mRNA.The transcriptional level of Cx43 fall-off gradually with the degree of malignancy,the content of Cx43 in tissue degrade which makes the low expression of Cx43. 3 The expression of PCNA is higher in glioma than in normal brain. The expression of PCNA tends to step up with histological anatomy grade of glioma.PCNA has close relationship with the malignant proliferation of glioma.4 The expression of PCNA in human brain glioma was positively related with the grade of tumor,and negatively related with the expression of Cx43mRNA and proten which hints that the expression of Cx43 gene has close relationship with malignant progression of glioma and the activity of the tumor cell proliferation.