Relationship Between Expression Of Bmi-1 And Telomerase In Esophageal Squamous Cell Carcinoma And Apoptosis

Background and objectives:Pathogenic factors of tumor are variety, but they can be traced the change of gene and metabolic enzymes correlated to cell. Esophageal cancer is a type of tumor and a process through the evolution of many stages, alteration and participation of many genes, alteration of metabolic enzymes associated with gene and (or) abnormal chang of mismatch-repair enzym of DNA. Protocarcinogenic gene Bmi-1 (Blymphoma Mo MLV insertion region, Bmi-1) is important regulating gene of Polycomb genes'family, Polycomb genes are composed by a variety of transcriptional repressor which related to cycle and proliferation of cell, therefore, PcG is a kind of important genes associated with development. Protocarcinogenic gene Bmi-1 is one of the core family member of PcG gene, its initial discovery and synergy with another cancer gene c-myc prompted cell transformation and tumor formation. Recent research has found that Bmi-1 as a kind of extensive expression nucleoprotein is very high correlation of Pathologic index with tumor occurrence, development, invasive and prognosis.Telomere is a special structure of chromosomal end, it is composed by many simple, short, repeat sequences and (telomere end-binding protein, TEBP). In normal human cells, telomeres become shortened following cell division gradually. Telomeres are essential and genetic components of the cell, because it can protect and compensate for the loss of genetic information in the end of chromosome and protect it won't be recognized by the nucleic acid enzyme and avoid degradation. The existence of telomeres is for maintaining the stability of chromosomes. The end of chromosomes will be exposed and susceptible to hydrolysize by exonuclease without telomere. Telomeres synthesis is not use DNA polymerases, but telomerase. Telomerase is special reverse transcriptase to synthesize DNA of telomere,it has dependence of RNA and is the ribosomal protein complex with nature of DNA polymerase, it could base on a template of his own RAN to synthesize telomerase sequences constantly and maintain the integrity of its chromosomal telomere.Division of normal cell each time will shorten the length of telomere, the the cell will be aging when telomere reduces to certain length ultimately. When the telomerase is present and in an activated state, the telomerase affects the length of telomere to be not shortened, thus the cell is immortalization. Especially in later stage of cancer and malignant tumor, activity of the telomerase enhance, making proliferation of large number of cancer cell, leading to deterioration and transfer of cancer cell. Currently, a large number of studies found that activation of telomerase is an important factor to promote occurrence, proliferation and metastasis of tumor, the expression level of telomerase has close relationship with occurrence, development, invasion, metastasis and prognosis of milignant tumor.In the most malignant tumors, Bmi-1 plays a significant role in their occurrence and development, oerexpressed Bmi-1 can activate transcriptase of reverse transcription of telomere, thereby it improved activity of the telomerase and the telomerase is matured enzyme in present research, more and more studies confirm the activity of telomerase in normal human tissues was inhibited and re-activated in cancer, activated telomerase may involve in malignant transformation. Current research indicates that the activated telomerase associated with occurrence and development of a variety of tumor. Therefore Bmi-1 and telomerase may have synergy in the process of occurrence and development of a variety tumor.Esophageal cance is malignant tumor which occurs in esophageal epithelium tissue and 2% of malignant tumor. China is a high incidence area of esophageal cancer and more common in the north than the south, Henan province is the highest incidence area, esophageal squamous cell carcinoma (squamous cell carcinoma SCC)commonly see, it mostly onsets at the age of 40 years old, but there is growing trend under the age of 40 in recent years, thus it becames a study hotspot in recent years. There have been relevant report at home and abroad that the expression level of Bmi-1 and telomerase in tumor cells, the relationship between them and apoptosis are worth for further study and exploration. This study applies the immunohistochemical SP method to detect the Bmi-1 and telomerase in normal esophageal mucosal epithelium, atypical growing tissue of cancr and the expression state in the tissue of esophageal squamous cell carcinoma; It analyzes apoptosis state in tissue of the the esophageal squamous cell carcinoma with TUNEL method, to study relationship between Bmi-1 and telomerase and occurrence, development and prognosis, transfer of esophageal squamous cell carcinoma, at the same time, to Explore the relationship of Bmi-1, telomerase and esophageal cancer cell, apoptosis simultaneouslyMethods1. Detected expression of Bmi-1, telomerase for 65 patients with esophageal squamous cell carcinoma,38 patients with atypical growing tissue of cancer,25 people with normal mucosa tissue with immunohistochemical SP method respectively, analyzed apoptosis state in tissue of the the esophageal squamous cell carcinoma with TUNEL method2. Statistical processing:statistical software SPSS 13.0 used for statistical analysis,χ2 test used for comparing of the strength expression of Bmi-1and telomerase, spearman rank correlation analysis formused for analyzing the relationship between two variables, the test indicated toα=0.05 level of significance test. Analysis of variance and t test used for comparing Apoptosis index (apoptosis index, AI), P<0.05 are significant.Results:1. Bmi-1 positive expression rates were increased in epithelium of normal mucosa group, atypical adjacent growing group and esophageal squamous cell carcinoma group were 20.00%(5/25),47.74%(17/38) and 64.62%(42/65) respectively, pairwise comparison of the three group, the differences were statistical significant (P<0.05). Positive expression rates of Bmi-1 in cancer tissue has no relationship with age, sex, diameter, depth of invasion, degree of differentiation, but it is related to lymph node metastasis and TNM stage of tumor. Bmi-1 positive expression rates of tumor without lymph node metastasis group rate was lower than those with lymph node metastasis group (χ2=6.460,P=0.011); Bmi-1 positive expression rates ofⅠ-ⅡA group was lower thanⅡB-Ⅲgroup (χ2=9.432, P=0.002).2. Telomerase protein postive expression rates in epithelium in normal mucosa group, atypical adjacent growing group and esophageal squamous cell carcinoma group were increased to 12.00%(3/25),52.63%(20/38) and 92.31%(60/65)) respectively, pairwise comparison of the three group, differences were statistical significant (P<0.05). Telomerase protein postive expression rates In cancer tissues was not related to age, sex, diameter, depth of invasion,degree of differentiation, but related to lymph node metastasis and TNM staging. telomerase protein postive expression rates in cancer without lymph node metastasis was lower than that with lymph node metastasis (χ2=8.125, P=0.004); Bmi-1 expression ofⅠ-ⅡA group was lower than thatⅡB-Ⅲgroup (χ2=8.125, P=0.004).3. Tumor cell apoptosis has relationship with the expression of Bmi-1 in esophageal squamous cell carcinoma. the tumor cell AI in Bmi-1 positive expression group was (5.35±2.33)%, it was lower than the negative expression group (13.41±5.62)%, the difference was significant (P<0.01).4. Tumor cell apoptosis in esophageal squamous cell carcinoma has relationship with telomerase expression. Tumor cells AI in telomerase-positive expression group was (6.35±2.33)%, it is lower than the negative expression group (15.52±5.94)%, the difference was statistical significant (P<0.01).5. The expression of Bmi-1 and telomerase in esophageal squamous cell carcinoma showed a positive correlation through the statistical analysis (P<0.05). Conclusions:1. Abnormal expression of Bmi-1, telomerase are closely related to the occurrence and development of esophageal squamous cell carcinoma. Bmi-1 and telomerase may have synergy in the process of occurrence and development of esophageal squamous cell carcinoma.2. The abnormal expression of Bmi-1 and telomerase in esophageal squamous cell carcinoma are significantly correlated to lymph node metastasis and TNM stage of tumor; it is indicated that the abnormal expression of Bmi-1 and telomerase are closely correlated to the invasion, metastasis and prognosis of esophageal squamous cell carcinoma.