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Neuro-Oncology 2004 6(1):9-14; doi:10.1215/S1152851703000279
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© 2004 by the Society forNeuro-Oncology

Expression of the splicing regulator polypyrimidine tract-binding proteinin normal and neoplastic brain

Ian E. McCutcheon1, Stephen J. Hentschel, Gregory N. Fuller, Wei Jin and Gilbert J. Cote

Departments of Neurosurgery (I.E.M., S.J.H.), Pathology (G.N.F.), and Endocrinology (W.J., G.J.C), The University of Texas M.D.Anderson Cancer Center, Houston, TX 77030, USA

1 Address correspondence to Ian E. McCutcheon, Department of Neurosurgery, M.D.Anderson Cancer Center, 1515 Holcombe Blvd., Box 442, Houston, TX 77030-4009(imccutch{at}mdanderson.org).


   Abstract

Polypyrimidine tract-binding protein (PTB) is a nuclear factor that bindsto the polypyrimidine tract of premRNA introns, where it is associated withnegative regulation of RNA splicing and with exon silencing. We havepreviously demonstrated that PTB expression is increased during glial celltransformation and that this increase correlates with changes in the RNAsplicing of the fibroblast growth factor receptor 1. In this paper we examinethe specific cellular distribution of PTB expression in normal brain and inglial and neuronal tumors. Paraffin sections were stained by using a primarymonoclonal antibody against PTB. Tissues that were analyzed included normalbrain (n = 2) and tumors of various types (low-grade astrocytoma, n = 2;anaplastic astrocytoma, n = 2; glioblastoma, n = 4; medulloblastoma, n = 4;central neurocytoma, n = 2; dysplastic gangliocytoma, n = 1; ganglioglioma, n= 1; paraganglioma, n = 1). In glial cell populations the majority ofastrocytes and oligodendrocytes were negative, but occasional positivelystaining cells were observed. Strongly positive PTB staining was observed inependymocytes, choroid plexus epithelium, microglia, arachnoid membrane, andadenohypophysis, and weak staining was found in the neurohypophysis. In allcases vascular endothelium and smooth muscle stained strongly. In tumorsamples, intense positive nuclear staining was observed in transformed cellsof low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme,medulloblastoma, paraganglioma, and the glial population of both gangliogliomaand dysplastic gangliocytoma (the neuronal cells of both were negative). Inmedulloblastoma, neoplastic neuronal cells were positive, as were other celllineages. In normal brain, all neuron populations and pineocytes were negativefor PTB. We conclude that although glial cells show derepression of PTBexpression, a similar mechanism is absent in both nonneoplastic neurons and inmost neuronally derived tumor cells. Strong upregulation of PTB expression intumor cells of glial or primitive neuroectodermal origin suggests involvementof this protein in cellular transformation. Whether PTB affects splicing ofRNAs critical to cellular transformation or proliferation is an importantquestion for future research.

Received May 28, 2003; Accepted August 26, 2003


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