title: Pathway alterations during glioma progression revealed by reverse phase protein lysate arrays.
abstract: The progression of gliomas has been extensively studied at the genomic level using cDNA microarrays. However, systematic examinations at the protein translational and post-translational levels are far more limited. We constructed a glioma protein lysate array from 82 different primary glioma tissues, and surveyed the expression and phosphorylation of 46 different proteins involved in signaling pathways of cell proliferation, cell survival, apoptosis, angiogenesis, and cell invasion. An analysis algorithm was employed to robustly estimate the protein expressions in these samples. When ranked by their discriminating power to separate 37 glioblastomas (high-grade gliomas) from 45 lower-grade gliomas, the following 12 proteins were identified as the most powerful discriminators: IBalpha, EGFRpTyr845, AKTpThr308, phosphatidylinositol 3-kinase (PI3K), BadpSer136, insulin-like growth factor binding protein (IGFBP) 2, IGFBP5, matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), phosphorylated retinoblastoma protein (pRB), Bcl-2, and c-Abl. Clustering analysis showed a close link between PI3K and AKTpThr308, IGFBP5 and IGFBP2, and IBalpha and EGFRpTyr845. Another cluster includes MMP9, Bcl-2, VEGF, and pRB. These clustering patterns may suggest functional relationships, which warrant further investigation. The marked association of phosphorylation of AKT at Thr308, but not Ser473, with glioblastoma suggests a specific event of PI3K pathway activation in glioma progression.
authors.affiliation: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.forename: Cristian
authors.initials: C
authors.lastname: Mircean
authors.forename: Ilya
authors.initials: I
authors.lastname: Shmulevich
authors.forename: David
authors.initials: D
authors.lastname: Cogdell
authors.forename: Yu
authors.initials: Y
authors.lastname: Jia
authors.forename: Ioan
authors.initials: I
authors.lastname: Tabus
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.forename: Janet M
authors.initials: JM
authors.lastname: Bruner
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000465:Algorithms; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000378:metabolism / Q000401:mortality; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D040081:Protein Array Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt