Expression And Significance Of PI3K/AKT/mTOR Pathway And Downstream Area In PRL Pituitary Adenomas

Pituitary adenomas are the most common tumors of neurosurgery, whichaccount for up to25%of all intracranial tumor, except gliomas andmeningiomas. These tumours are mostly benign, but cause significantmorbidity through mass effects and/or the inappropriate secretion of pituitaryhormones. Now a better classification is based on form and function ofpituitary adenomas, including PRL-producing adenomas, GH-producingadenomas, ACTH-producing adenomas, TSH-producing adenomas,gonadotroph adenomas, Multiple secretory cell adenomas, nonfunctioningadenomas and Malignant pituitary adenomas. PRL-producing adenomas arethe most common type, which account for about40%to60%of all pituitaryadenomas. There are obvious gender differences in PRL-pituitary adenoma,including the age of onset and clinical symptoms PRL-producing adenomasare more common in females, who tend to present at a younger age withhormonal disturbances. In contrast, men tend to present later with largertumors that more often result in mass effects and hypopituitarism secondary toadenohypophysial destruction. Therefore, it is necessary to study thesex-related differences in PRL-producing adenomas. A major signallingpathway responsible for regulating cell growth and proliferation, downstreamof growth factor receptors, is the phosphatidylinositol3-kinase (PI3K)/Aktpathway. This pathway is studied in a variety of tumors. In this experiment,we will study the expression of PI3K/Akt/mTOR pathway and its downstreamarea in PRL-producing adenomas.Objective: To study the sex-related difference in expression ofPI3K/Akt/mTOR pathway and its downstream area in PRL-producingadenomas, including PI3K, p-PI3K, AKT, p-AKT, p-mTOR, p70S6K and4E-BP1. Methods: In this experiment, to observe PRL pituitary adenoma by HEstaining and study the protein expression of PI3K, p-PI3K, AKT, p-AKT,p-mTOR, p70S6K and4E-BP1which were detected by Western blot. We willdiscuss expression of PI3K, AKT, mTOR, p70S6K and4E-BP1of mRNAwhich were detected by semi-quantitative PCR in PRL-producing adenomas.Results:(1) HE staining showed that microscopic features of theexperimental tumor tissues were consistent with PRL-pituitary adenomas.(2)Western blot results show that the proteins expression of PI3K, p-PI3K, AKT,p-AKT, p-mTOR, p70S6K and4E-BP1existed in all patients withPRL-producing adenomas. And the protein expression levels of PI3K andp-PI3K of PRL-producing adenomas in the male patients (1.098±0.056and0.393±0.028) were higher than female (0.775±0.025and0.043±0.002).Results had statistical significance (P<0.01). The protein expression level ofAKT of PRL-producing adenomas in the male patients (1.190±0.050) washigher than female (0.855±0.057). Results had statistical significance(P<0.05). The protein expression level of p-AKT of PRL-producing adenomasin the male patients (0.745±0.024) was higher than female (0.113±0.026).Results had statistical significance (P<0.01). The protein expression level ofp-mTOR of PRL-producing adenomas in the male patients (1.097±0.044) washigher than female (0.732±0.020). Results had statistical significance(P<0.01). The protein expression levels of p70S6K and4E-BP1ofPRL-producing adenomas in the male patients (1.243±0.063and1.156±0.003)were higher than female (0.797±0.030and0.836±0.034). Results hadstatistical significance (P<0.01). The proteins expression of p-PI3K, p-AKTand p-mTOR existed in all patients with PRL-producing adenomas, show thatPI3K/AKT/mTOR signaling pathway was activated in patients withPRL-producing adenomas. And the protein expression levels of p-PI3K,p-AKT and p-mTOR of PRL-producing adenomas in the male patients werehigher than female. Results had statistical significance (P<0.01). It is showthat the PI3K/Akt/mTOR signaling pathway was more activation in malepatients with PRL-producing adenomas.(3) Semi-quantitative PCR results show that the expression of PI3K, AKT, mTOR, p70S6K and4E-BP1ofmRNA in PRL-producing adenomas in the male patients were higher thanfemale.Conclusions: The proteins expression of PI3K, p-PI3K, AKT, p-AKT,p-mTOR, p70S6K and4E-BP1existed in all patients with PRL-producingadenomas. And the proteins expression of PI3K, p-PI3K, AKT, p-AKT,p-mTOR, p70S6K and4E-BP1were higher in male patients than female withPRL-producing adenomas. It is show that the PI3K/Akt/mTOR signalingpathway was more activation in male patients with PRL-producing adenomas.(2) The expression of PI3K, AKT, mTOR, p70S6K and4E-BP1of mRNAexisted in all patients with PRL-producing adenomas. And the expression ofPI3K, AKT, mTOR, p70S6K and4E-BP1of mRNA in PRL-producingadenomas in the male patients were higher than female. Once again, it is showthat the PI3K/Akt/mTOR signaling pathway was more activation in malepatients with PRL-producing adenomas. In summary, we believe that thePI3K/Akt/mTOR signaling pathway and its downstream factors are moreactivation in male patients with PRL-producing adenomas.