Expressions of VEGF, PTEN, and downstream signaling pathways in invasive pituitary adenomas
MAO Jianhui1, SUN Zhaosheng1, GUO Hong1, WEI Jianhui1, SI Na1, QIU Lei2, GUO Lianfeng3, and ZHENG Lei4
1.Department of Neurosurgery, 2.Department of Pathology, 3.Department of Clinical Laboratory, 4.Central Laboratory, Harrison International Peace Hospital, Hengshui 053000, China
Abstract：Objective To analyze the expressions of vascular endothelial growth factor (VEGF), gene of phosphate and tension homology deleted on chromosome ten (PTEN), and downstream signaling pathways in invasive pituitary adenomas.Methods Sixty-two cases of pituitary adenomas (32 invasive and 30 non-invasive tumors) and 60 cases of normal pituitary glands were selected. The expressions of PTEN/VEGF, their downstream phosphate-serine/threonine kinase (p-Akt) and phosphate-mitogen-activated protein kinase (p-MAPK) signaling pathways in all the pituitary adenomas and normal pituitary glands were detected by quantitative polymerase chain reaction and Western blot.Results (1)There was a significant decrease of PTEN and notable increase of VEGF in patients with pituitary adenomas compared to the normal controls(P<0.05). Meanwhile, the expression levels of PTEN (0.42±0.10)and VEGF(3.61±0.16) in the invasive pituitary adenomas were significantly different from those in the non- invasive pituitary adenomas (PTEN 0.86±0.11, VEGF 2.06±0.13) (PTEN t=6.31,P<0.05; VEGF t=10.60, P<0.05).(2) Levels of p-Akt and p-MAPK in the pituitary adenoma group were notably increased compared with the control group(P<0.05), whereas the invasive pituitary adenomas(p-Akt 3.90±0.14; p-MAPK 2.52±0.11) showed a statistically significant increase compared with the non- invasive pituitary adenomas(p-Akt 2.27±0.11; p-MAPK 1.89±0.05)(p-Akt, t=12.95, P<0.05; p-MAPK t=7.29, P<0.05).Conclusions Our study has offered evidence that there is a significant decrease of PTEN and notable increase of VEGF, p-Akt and p-MAPK in invasive pituitary adenomas, suggesting that these changes may be related to the invasiveness of pituitary adenomas. These findings can facilitate the diagnosis and treatment of invasive pituitary adenomas.
Molitch M E. Diagnosis and treatment of pituitary adenomas: a review[J]. JAMA,2017, 317(5):516-524.
[4]
Zhou K,Zhang T,Fan Y, et al. Micro RNA-106b promotes pituitary tumor cell proliferation and invasion through PI3K/AKT signaling pathway by targeting PTEN[J]. Tumour Biol, 2016, 37(10):13469-13477.
[5]
Wise H M,Hermida M A,Leslie N R. Prostate cancer, PI3K,PTEN and prognosis[J]. Clin Sci (Lond),2017, 131(3):197-210.
[6]
Rubinfeld H, Shimon I. PI3K/AKT/mTOR and Raf/MEK/ERK signaling pathways perturbations in non-functioning pituitary adenomas[J]. Endocrine, 2012, 42:285-291.
[7]
Li K K, Xia T,Ma F M,et al.MiR-106b is overexpressed in medulloblastomas and interacts directly with PTEN[J]. Neuropathol Appl Neurobiol, 2015, 41:145-164.
Xue L,Huang J,Zhang T, et al. PTEN inhibition enhances angiogenesis in an in vitro model of ischemic injury by promoting Akt phosphorylation and subsequent hypoxia inducible factor-1α upregulation[J]. Metab Brain Dis,2018, 33(5):1679-1688.
[10]
Huang J, Kontos C D. PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects[J]. J Biol Chem, 2002, 277(13):10760-10766.
[11]
Meta E,Brullo C,Sidibe A, et al. Design, synthesis and biological evaluation of new pyrazolyl-ureas and imidazopyrazolecarboxamides able to interfere with MAPK and PI3K upstream signaling involved in the angiogenesis[J]. Eur J Med Chem,2017, 133:24-35.
[12]
Tena M L, Ortiz P A, Vega H A. Phosphatase and tensin homologue and pituitary tumor-transforming gene in pituitary adenomas. clinical-pathologic and immunohistochemical analysis[J]. Ann Diagn Pathol, 2008, 12:275-282.
[13]
Park J H,Yoon J,Park B. Pomolic acid suppresses HIF1α/VEGF-mediated angiogenesis by targeting p38-MAPK and mTOR signaling cascades[J]. Phytomedicine,2016, 23(14):1716-1726.
2019, Vol. 30 
