Increased STAT-3 and synchronous activation of Raf-1-MEK-1-MAPK, and phosphatidylinositol 3-Kinase-Akt-mTOR pathways in atypical and anaplastic meningiomas.
The intracellular events promoting meningioma cell proliferation in high grade tumors are not established. In this study we compared 45 WHO grade I and 35 grade II or III meningiomas by Western blot or immunohistochemistry for phosphorylation/activation of the MEK-1-MAPK, PI3 K-Akt-mTOR-PRAS40 and STAT3 pathways. By Western blot, STAT3 activation was detected in 75% of grade I compared to 100% of grade II and III meningiomas. By immunohistochemistry p-STAT3 was detected in 28% of grade I compared to 65 or 66% of grade II and III meningiomas, respectively. Phosphorylated MEK-1 and p-MAPK were activated in nearly all grade I, II and III tumors. Phosphorylated Akt was also detected in the majority of meningiomas of each grade although downstream pathway component activation was less widespread. These findings suggest that there is increased STAT3 activation in WHO grade II and III meningiomas compared with grade I tumors. Moreover, each of the three major growth regulatory pathways is concomitantly activated in higher grade meningiomas.
Johnson
Mahlon D
MD
Division of Neuropathology, Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA. mahlon_johnson@urmc.rochester.edu
O'Connell
Mary
M
Vito
Fran
F
Bakos
Robert S
RS
D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008577:Meningeal Neoplasms / Q000201:enzymology* / Q000473:pathology; D008579:Meningioma / Q000201:enzymology* / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D050796:STAT3 Transcription Factor; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human