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Expression of the splicing regulator polypyrimidine
tract-binding protein in normal and neoplastic brain
McCutcheon IE, Hentschel SJ, Fuller GN, Jin W, Cote GJ
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
Polypyrimidine tract-binding protein (PTB) is a nuclear factor that binds to
the polypyrimidine tract of pre-mRNA introns, where it is associated with
negative regulation of RNA splicing and with exon silencing.
We have previously demonstrated that PTB expression is increased during glial
cell transformation and that this increase correlates with changes in the RNA
splicing of the fibroblast growth factor receptor 1.
In this paper we examine the specific cellular distribution of PTB expression in
normal brain and in glial and neuronal tumors.
Paraffin sections were stained by using a primary monoclonal antibody against
PTB.
Tissues that were analyzed included normal brain (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 of astrocytes and oligodendrocytes were
negative, but occasional positively staining cells were observed.
Strongly positive PTB staining was observed in ependymocytes, choroid plexus
epithelium, microglia, arachnoid membrane, and adenohypophysis, and weak
staining was found in the neurohypophysis.
In all cases vascular endothelium and smooth muscle stained strongly.
In tumor samples, intense positive nuclear staining was observed in transformed
cells of low-grade astrocytoma, anaplastic astrocytoma, glioblastoma multiforme,
medulloblastoma, paraganglioma, and the glial population of both ganglioglioma
and dysplastic gangliocytoma (the neuronal cells of both were negative).
In medulloblastoma, neoplastic neuronal cells were positive, as were other cell
lineages.
In normal brain, all neuron populations and pineocytes were negative for
PTB.
We conclude that although glial cells show derepression of PTB expression, a
similar mechanism is absent in both nonneoplastic neurons and in most neuronally
derived tumor cells.
Strong upregulation of PTB expression in tumor cells of glial or primitive
neuroectodermal origin suggests involvement of this protein in cellular
transformation.
Whether PTB affects splicing of RNAs critical to cellular transformation or
proliferation is an important question for future research.
© 2003 Duke University Press
Source: http://caliban.ingentaselect.com/vl=5592864/cl=22/nw=1/rpsv/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n1/s2/p9
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