Study Of The Expression And Regulation Mechanisms Of Seladin-1, P53, Mdm2 In Human Pituitary Adenomas

Objectives:To study the expression of seladin-1,p53 and mdm2 in different types of human pituitary adenomas,to analyze the relationships with types,clinical features(including age,tumor size,invasion,recurrence and apoplexy),proliferation and apoptosis of tumor cells,to investigate the role of p53/Mdm2 auto-regulatory feedback-loop and its relationship with seladin-1,and explore the role of p53 gene network in tumor formation and developing.These studies may provide theoretical foundation for gene therapy of pituitary adenomas.Methods:Seladin-1,p53 and mdm2 in fifty pituitary adenoma specimens were detected by SYBR Green I Real-time RT-PCR.In addition,PCNA(proliferating cell nuclear antigen)of fifty pituitary adenoma specimens were detected by immunohistochemistry and their apoptosis were detected by TUNEL.PCNA labeling indices(PCNALI)and apoptotic labeling indices(ALl)were calculated to quantify proliferation and apoptosis.Finally,undertake statistical analysis according to experimental purposes.Results:1.There were close relationships between the expression of PCNA and the diameter,invasion and recurrence of pituitary adenomas,while ALI was correlated to tumor size and invasion.Neither PCNALI nor ALl was influenced by gender,age, tumor texture,apoplexy,cystic degeneration and pathology types.There was a correlation between PCNALI and ALl(r=0.53,P＜0.05).2.The mRNA expression level of p53 in the non-functioning pituitary adenomas was significantly higher than that of the PRL and multi-functioning pituitary adenomas,while the level of p53 in the GH pituitary adenomas was significantly greater than that of the PRL, multi-functioning and non-functioning pituitary adenomas.The expression levels of p53 in the invasive and the recurrent groups were significantly higher than that in the non-invasive and non-recurrent groups.The expression level of p53 in the macroadenoma group was lower than that in the huge adenoma and the microadenoma groups.P53 didn't have a correlation with PCNALI and ALI.3.The mRNA expression level of mdm2 in the non-functioning pituitary adenomas was significantly larger than that in the PRL,GH and multi-functioning pituitary adenomas,while the level of p53 in the GH pituitary adenomas were significantly less than that in the PRL,multi-functioning and non-functioning pituitary adenomas.The expression levels mdm2 in the invasive and recurrent groups were significantly higher than in the non-invasive and non-recurrent groups.The macroadenomas had a greater expression level of mdm2 than huge adenomas and microadenomas.PCNALI and ALI weren't correlated to a higher expression level of mdm2.4.There was a correlation between p53 and mdm2(r=0.47,P＜0.05).5.The mRNA expression level of seladin-1 in the non-functioning pituitary adenomas were significantly larger than that of the PRL,GH and multi-functioning pituitary adenomas.The expression levels seladin-1 in the invasive and recurrent groups were significantly higher than that in the non-invasive and non-recurrent groups.There was an increasing growth in seladin-1 expression with the tumor size increase.Seladin-1 had a correlation with PCNALI neither ALI.6.Seladin-1 had a correlation with p53(r=-0.32, 0.02＜P＜0.05)and mdm2(r=0.29,P＜0.05).Conclusions:1.The expression level of PCNA reflected the proliferative activity, the pathological nature and the invasive biological behavior of the pituitary adenomas. Pituitary adenomas with high PCNA level had great tendency of recurrence.There was spontaneous cell apoptosis in pituitary adenomas,which was an important biological characteristic of pituitary adenomas.Apoptotic cells of pituitary adenomas rised with the increase in proliferative activity,which implied the balance regulation between proliferation and apoptosis.2.P53 was in accordance with mdm2, meanwhile they had independent mechanism of action,which lead to complicated manifestations between different individuals and growth stages.3.Seladin-1 affected p53 and mdm2,and seladin-1,p53 and mdm2 in human pituitary adenomas closely correlated with its invasiveness and proliferation,and may play an important function in pituitary adenomas.4.An interactive circuit loop was made up by Seladin-1,P53 and Mdm2,and seladin-1 play a key role in it.If can seladin-1 be suppressed,the interactive circuit loop would be blocked,which may obstruct the p53/Mdm2 auto regulatory feedback-loop and tumorigenesis.