Expression Of Cyclinb1 And Cdc25b In The Human Uterine Cervix Cancers And Their Clinical Significance

BackgroundThe cervical cancer is one of the most familiar gynecology malignant tumors, only next to mammary glands cancer in the global women malignant tumor outbreak rate,be placed in the second.Although the cervical cancer of the earlier period examine a patient to develop with treatment very quickly,the outbreak rate of the cervical cancer at some nations and the region have augmentative trend in recent years,especially to young turn a development.And,on the clinic,young or later period the another case combine not a few see.Therefore have a necessity to study the outbreak mechanism of the cervical cancer further,understand the biology behavior of the cervical cancer for the clinic,instruction the treatment provide a help.Cyclin(the cell cycle protein),because it is in the cell period synthesizes continuously a backlog continuously and the activity appear the periodic variety,is a set of structure is similar,can combine and regulate CDK(cyclin dependent kinase) of protein,know together as the cyclin family,currently have 8 kinds of members, named cyclinA,B,the C…H.Each kind of type with several isoforms.As regulatory subunit,they need combine different catalytic subunit to form the compound(cyclin-CDK), thus to modify the function protein phosphorily,and control the cell cycle to carry on.The cyclinB gene of human,is cloned sucessfully from Hunter etc.in 1989. cyclinB-cdc2 compound is the importance constitute part of M period promote factor(the M phase-promoting factor) or called the maturity promote the factor MPF(the maturation-promoting factor).The CyclinB1 is one of the main components to control the cell cycle G2/M restriction.The CDC25 family of phosphatases is belongs to the CDK(cyclin-dependent protein kinase) reactivator family,including CDC25A,CDC25B,CDC25C,can activate the cyclin/CDKs in different points of cell cycle,influent the check points: G₁/S and G₂/M And the CDC25B for the transition of G₂/M is imperative.CDC25B express in the all cell circle,have tumorcology in some special condition,accumulate in S phase,peak amplitude in M phase,and phosphorylated by CDK1-cyclin A,, degradated by ubiquitin proteasome pathway(UPP).CDC25B are responsible for the dephosphorylation of pThr14 an pTyr15 and thereby trigger the final activation of the Cdk/cyclin complexes,make CDK1 from non-active condition of high phosphorylation to active condition of low phosphorylation,accecelarte the cell caryocinesia.CDC25B is a member of the CDC25 family of phosphatases.CDC25B activates the cyclin dependent kinase CDC2 by removing two phosphate groups and it is required for entry into mitosis.CDC25B shuttles between the nucleus and the cytoplasm due to nuclear localization and nuclear export signals.The protein is nuclear in the M and G₁ phases of the cell cycle and moves to the cytoplasm during S and G₂.CDC25B has oncogenic properties,although its role in tumor formation has not been determined.Multiple transcript variants for this gene exist.The three human Cdc25s,Cdc25A,Cdc25B,and Cdc25C,Cdc25B and Cdc25C are regulators of G₂/M through their activity on Cdk2/cyclin A,Cdk1/cyclinA,and Cdk1/cyclin B.Objective:Expression of CDC25B and CyclinB1 proteins in cervical carcinoma have been evaluated and then correlated to the clinical pathological character of patients,which study the relationship between significance of proliferation and apoptosis in cervical carcinoma and then explore the mechanism of cervical carcinoma.Materials:Collect paraffin imbedding uterine cervix tissues of 25 cases of precancerous lesions and 67 cases of uterine cervix cancers patients,who had pathological and clinical integrity data and underwent gynecological operation at the Department of Gynecology,the First Affiliated Hospital,Zhengzhou University,from 2005 to 2007. All the patients didn't get any radiotherapy,chemotherapy and other therapy before operation.Among them,there are 8 CIN(cervical intraepithelial neoplasias)â… ,8 CINâ…¡,11 CINâ…¢,11 well-differentiated SC(squamous cell carcinoma),11 moderately differentiated SC,29 poorly differentiated SC,and 9 lymphatic metastasis, 6 adenocarcinoma.Methods:Using immunohistochernistry method of SABC detected the expression of CDC25B proteins and immunohistochernistry method of SP detected the expression CyclinB1 proteins in 10 cases of normal uterine cervix tissues,25 cases of precancerous lesions and 67 cases of uterine cervix cancers,and analysed the relationship with age,texture category,hietological type pathological grading,clincal staging and lymphatic metastasis.The differences of CyclinB1 and CDC25B protein expression were assessed by Chi-Square test.The correlation between their expression and clinical and pathological parameters were assessed by Chi-Square test and Fisher exact probabilistic method.The test standard wasα=0.05.Statistical analysis was performed by statistics software SPSS13.0 package.Results1.According to immunohistochemistry results in 90 ovarian tissues,the positive rate of CyclinB1 protein expression in normal uterine cervix tissues,precancerous lesions and uterine cervix cancers 20%,64%,88%respectively,the positive rate of CDC25B protein expression in normal uterine cervix tissues,precancerous lesions and uterine cervix cancers were 0%,40%,43%respectively.The expression of CyclinB1 and CDC25B protein in precancerous lesions and uterine cervix cancers was significantly higher than that in normal uterine cervix tissues (P＜0.05).2.Expression of CyclinB1 proteins was increased with ages and hietological type pathological grading(P＜0.05),but was no significantly correlate with txture category,clincal staging and lymphatic metastasis(P＞0.05).Expression of CDC25B protein was increased with ages and clincal staging also increased in the tumor tissues from the patients with local lymphatic metastasis(P＜0.05),but was no correlate with hietological type pathological grading(P＞0.05).3.The correlation between the expression of CyclinB1 and CDC25B protein in uterine cervix tissues:The correlation index was 0.299,P＜0.05.There was positive correlation between the expression of CyclinB1 and CDC25B protein in uterine cervix tissues.Conclutions1.The expression of CyclinB1 proteins in the precancerous lesions and uterine cervix cancers was higher than that in normal uterine cervix tissues(p＜0.05),The abnormal expression of CyclinB1 protein might play an important role in carcinogenesis and progression of uterine cervix carcinoma.Its expression have relations with ages and histological grade.Because the histological grade is closely related with the prognosis of cervical cancer,the detection of cyclinB1 can be used as the evaluation of patients with cervical cancer and the prognosis of survival.2.The expression of CDC25B proteins in the precancerous lesions and uterine cervix cancers was higher than that in normal uterine cervix tissues(p＜0.05),and suggest that it participate in the process of the development of cervical cancer.Its expression have relations with ages,clincal staging and local lymphatic metastasis, play an important role in the infiltration and metastasis of carcinomas.3.The expression of CyclinB1 and CDC25B may play an commom role on the level of cell cycle,especially in the G₂/M checkpoint,take an important role in the carcinogenesis and progression of uterine cervix carcinoma.CyclinB1 and CDC25B proteins were higher expressed in the precancerous lesions and uterine cervix cancers,and they were positive correlate in them;CyclinB1 and CDC25B may be the new aim of diagnosis and therapic of the precancerous lesion and uterine cervix cancer.