Expression Of P110α And P85α Subunits In PI3K In Invasive And Non - Invasive Non - Functional Pituitary

Background:Invasive non-functioning pituitary adenoma (NFPA) is a benign and heterogeneous group among pituitary adenoma. Complete resection of tumor is difficult due to its large size and invasiveness. Radiotherapy is effective in some patients in reducing the size of NFPA remnant, but also incurs multiple complications such as hypopopituitarism, optic neuropathy and neurocognitive dysfunction. Thus, targeted therapy provides a novel direction for the treatment of NFPA. The PI3K/AKT/mTOR pathway is a signal transduction cascade involved in cell growth and metabolism, and plays an important role in cancer development. PI3K can be divided into three classes among which Class I is a heterodimer consisting of a catalytic subunit (p110α,p110β, p110γ and p110δ) and a regulatory unit. Inhibitors of PI3K subunits have been studied in multiple tumors. As far as we are concerned, there is no research on expression levels of PI3K subunits.Methods:NFPAs were obtained from 32 patients, among which 14 were invasive NFPA (5 men and 9 women; 45.5+6.5 years), and 15 were non-invasive NFPA (9 men and 6 women; 53.0±13.0 years), and 3 were normal pituitary (1 men and 2 women; 58.0 years) who underwent endoscopic transsphenoidal surgery between December 2012 and August 2014 at Neurosurgery Department of Peking Union Medical College Hospital. Immunohistochemistry, Western Blotting and qRT-PCR were applied to determine the expression levels of p110α and p85a subunits of PI3K, PTEN and Akt in three types of samples abovementioned.Results:Immunohistochemistry found that the expression of p110α in pituitary tissue was significantly higher compared with invasive group (p<0.05). The expression of PTEN in non-invasive group was significantly higher than that of the pituitary tissue and invasive group (p<0.05). Akt staining found that the expression of Akt in invasive group (p<0.05) and non-invasive group (p<0.001) was significantly increased compared with pituitary tissue. And non-invasive group increased more significantly than invasive group (p<0.01). Western Blotting revealed that p85a increased significantly in invasive group (p<0.05) compare with pituitary tissue. qRT-PCR of mRNAs for p110α,p85 α,PTEN and Akt showed no significant difference among three groups.Conclusion:In our research, we find that p110α is underexpressed and p85 a is overexpressed in invasive NFPA, which provides an experimental basis for the research of PI3K targeted drugs for NFPA. The expression of other subunits of PI3K deserves further studving.