The Expression Of P110α And P85α Of PI3K-Akt-mTOR Signaling Pathway Is Associated With The Invasion Of Nonfunctional Pituitary Adenomas

Objective:To detect the expression of p110α and p85a Subunits of PI3K and AKT and the negative regulator of PI3K-Akt-mTOR Signaling Pathway——PTEN in nonfunctional pituitary adenomas (NFPAs). And to investigate the relationship between them and the invasion of NFPAs.Methods:Pituitary adenomas specimens were obtained from patients who underwent endoscopic transsphenoidal surgery between December 2012 and August 2014 at Neurosurgery Department of Peking Union Medical College Hospital.31 patients who were diagnosed with NFPAs based on clinical, radiological and pathological data were included in this study. There were 15 patients in the invasive NFPAs (6 men and 9 women; 45.5±6.5 years) and 16 non-invasive NFPAs (9 men and 7 women; 53.0±13.0 years). All patients were first surgeries and those patients who had received previous radiation therapy were not included in this study. In addition, there were 3 normal pituitary (1 men and 2 women; 58.0 years) as normal control that came from the body donation. All of the donors died of non-neurological and nonendocrine diseases. In this study, grade 4 tumors according to the Knosp classification were considered to invasive NFPAs while grade 0 tumors with round body and size between 20mm and 30mm were regarded as non-invasive NFPAs. Immunohistochemistry and qRT-PCR were applied to determine the expression levels of p110α and p85a, AKT, p-AKT and PTEN in three types of samples above mentioned. SPSS17.0 software was used to analyze the data. Differences between groups were determined by one-way analysis of variance and the two independent samples t-test. P< 0.05 was defined as statistically significant.Results:Immunohistochemistry found that the expression level of p85a in invasive group was significantly lower compared with non-invasive group (p<0.05) or normal pituitary tissue (p<0.05). While the protein expression level of p110α in nonfunctional pituitary adenomas group was significantly higher than that of normal pituitary tissue(p<0.05) and the expression level of p110α between invasive group and non-invasive group has no significant difference(p>0.05). The expression level of PTEN in nonfunctional pituitary adenomas group was significantly lower compared with normal pituitary tissue (p<0.05), but there was no significant difference between invasive group and non-invasive group(p>0.05). And the protein expression level of AKT in nonfunctional pituitary adenoma group was significantly higher than that of normal pituitary tissue(p<0.05), and the expression level of AKT in invasive group was also significantly higher than non-invasive group tissue(p <0.05). The p-AKT protein level in invasive group was significantly higher than non-invasive group tissue(p<0.05) and normal pituitary tissue(p<0.05). On the other hand, the AKT was over-activated in invasive group, but in non-invasive group there was no significant difference between the level of AKT and p-AKT (p>0.05). qRT-PCR of mRNAs level for p85a in that of normal pituitary tissue was significantly higher than nonfunctional pituitary adenomas group(p<0.05), but there was no significant difference(p>0.05) between invasive group and non-invasive group. The mRNA level of p110α in nonfunctional pituitary adenomas group was significantly higher than that of normal pituitary tissue(p<0.05), and there was no significant difference between invasive group and non-invasive group(p>0.05). PTEN mRNA level in that of normal pituitary tissue was significant lower compared to nonfunctional pituitary adenoma group(p<0.05). But there was no significant difference between invasive group and non-invasive group(p>0.05). AKT in nonfunctional pituitary adenoma group was significantly higher than that of normal pituitary tissue(p<0.05). But there was no significant difference between the non-invasive group and the invasive groups(p>0.05).Conclusion and Significance:In our research, we found that the protein expression level of p110α subunit and AKT was significant higher and AKT was over-activated in invasive NFPAs than that of normal pituitary tissue, while p85a subunit and PTEN was under-expressed. And the higher expression of p110α subunit and the lower expression of p85a subunit is related with the invasion of nonfunctional pituitary adenomas. What is more, the over-activation of AKT in PI3K-Akt-mTOR Signaling Pathway may be due to the higher expression of p110α subunit and the lower expression of p85a subunit.