| Oncogenesis is a multistep and multifactorial process in the geneticand epigenetic levels , which results in uncontrolled cell proliferation ,transfor-mation and cell death.Phosphorylation of proteins on serine or threonine residues preceding pro-line(Ser/Thr-Pro)is an important signal mechanism controlling many cellular processes,such as cell cycle regulation,cell differentiation and proliferation.The conformation and function of phosphorylated Ser/Thr-Pro motifs are further regulated by the prolyl isomerase Pinl . The overexpression of Pinl is involved in the tumor development and progression. Cyclin D1 is a checkpoint of Gl/S transition. Inhibition of Cyclin D1 causes cells arrest in G1 phase, which suppresses tumor cells growth. Studies have demonstrated that Cyclin D1was overexpressed in many tumors.In this study, the expressions of Pinl and Cyclin D1 in normal ovarian and epithelial ovarian tumors were detected by immunohistochemistry to explore the expression of Pinl and its relationships with Cyclin D1 in ovarian cancer, Their function in the leukemogenesis was further discussed.Material and Method1. Samples161 epithelial ovarian cancer tissue samples ( 97 ovarian cancers,40 borderline ovarian tumors,24 benign tumors of ovary)and 25 normal ovary tissue samples were obtained from patients who had surgery in the LiaoNing Province Tumor Hospital , Fengtian Hospital Affiliated to Shenyang Medical College ,the fifth Hospital of Shenyang,Shenyang 202 Hospital between 2001 and 2007, which were fixed in 4% paraformaldehyde and embedded in paraffin.2. Reagents and sourceThe Pinl polyclonal antibody was provided by Santa Cruz Company of America. The Ultro-sensitive SP kit,the Cyclin D1 antibody,AEC agent kit and the goat-anti-rabbit second antibody were bought from Boster Biological Company of Wuhan.3.MethodsPinl, Cyclin D1 were detected by immunohistochemistry S-P。Result determination:①Pinl:The normal staining was in the nucleus;the overexpressed staining was in the nucleus and/or cytoplasm.A:The staining intensity was scorded as negative(0) , weak(1) , moderate(2) , and strong(3);B:The number of cells stained was graded as follows : <25 % ;0,25%-49%;1,50%-74% ;2,≥75%;3. AxB,Grades≥3 showed its overexpression.②CyclinDl was a nucleus and(or)cytoplasm staining protein.Less than 10% of tumor cells showed negative,and over 10% of tumor cells showed positive.4. Statistical analysisAll the data were analyzed by PEMS 3 .1 medical statistics software.X2-test was used to compare the clinicopathological characteristics with the expression of Pinl and CyclinDl .The statiscal significance was defined as P<0. 05.Results1 .Expression of Pinl and CyclinDl in ovarian tissues Pinl was weak or no expression in normal ovary tissue cells .It was stained moderately or strongly in benign ovarian tumors and borderline ovarian tumors. In ovarian cancers it was stained strongly in cytoplasm besides in nucleus. The expression of Pin1 was higher and higher in normal ovrarian tissues, benign ovarian tumors, borderline ovarian tumors and ovarian cancers. There was significant difference after x2 test. Pin1 was overexpressed in 61.86% ovarian cancers. CyclinDl was not expressed in normal ovarian tissue cells,and was expressed in nucleus and cytoplasm of the ovarian tumors cells.The rates of cyclinDl were gradually higher in normal ovrarian tissues, benign ovarian tumors, borderline ovarian tumors and ovarian cancers. 59.8% ovarian cancers were positive.2. The relationship of Pin1 and Cyclin D1 between expression and characteristics of clinical pathology in ovarian cancers.There was no significant correlation between the expression of Pin1 and age,histological type, differentiation, lymph node metasis and P-TNM stage of patients. There was positive correlation between the expression of Cyclin D1 and clinical differentioation, and no significant relation of the types of tissue,age,lymph node metasis and P-TNM stage of patients.3. The correlation between expression of Pin1 and cyclinDl in epithelial ovarian tumors45 cases were positive expression of cyclinD1 in 60 cases of ovarian cancers of over expression of Pin1, 24 cases were negative expression of cyclinD1 in 37cases of ovarian cancers of lower expression of Pin1. There was positive significant correlation between Pin1 and cyclinD1 in ovarian cancers. (x2=15.13, P<0.01)Conclusions1 .The level of Pinl in the tumor tissues is noticeably higher than that in the normal tissues. The level of cyclinDl in the tumor tissues is noticeably higher than that in the normal tissues.2. The expression of Pinl protein was not related to age,histological type, differentiation and P-TNM stage. The expression of cyclinDl protein was related to differentiation,but not related to age, histological type,differentiation and P-TNM stage.3 .This study showed that Pinl level correlated with Cyclin D1 positively, which suggests that up-regulation of Pinl enhances the expression of Cyclin D1, acting as an upsteam factor of Cyclin D1. |
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