Polypyrimidine tract binding protein and Notch1 are independently re-expressed in glioma.
Polypyrimidine tract binding protein (PTB) is expressed in developing mammalian astrocytes, absent in mature adult astrocytes, and aberrantly elevated in gliomas. It is unclear whether PTB is a coincidental marker of tumor progression or a significant mediator of tumorigenesis. In developing Drosophila, the absence of the PTB homolog, hephaestus, results in increased Notch activity. Since Notch is a well-known inducer of glial cell fate, we determined whether overexpression of PTB in glial cell tumors provides a selective growth advantage by inhibiting activated Notch (Notch1IC)-mediated differentiation. To do this, we performed an immunohistochemical analysis for expression of PTB, activated Notch1 (Notch1IC), Hes1 (a Notch target), and GFAP on an extensive human tissue microarray that included 246 gliomas, 10 gliosarcomas, and 10 normal brains. Statistically significant PTB overexpression was seen in all glioma grades, with the highest increase in grade IV tumors. Notch1IC was also abnormally expressed in gliomas except in a subset of grade IV tumors in which it was absent. This decrease in Notch1IC was not associated with increased PTB expression. We conclude that PTB, and Notch1 serve as independent and functionally unlinked markers of glioma progression.
Cheung
Hannah C
HC
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, 77030, USA.
Corley
Lynda J
LJ
Fuller
Gregory N
GN
McCutcheon
Ian E
IE
Cote
Gilbert J
GJ
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D009367:Neoplasm Staging; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D038941:Polypyrimidine Tract-Binding Protein; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C497761:NOTCH1 protein, human; C078493:HES1 protein, human