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Tumor Biology |
Ludwig Institute for Cancer Research (O.B., F.B.F., H.-J.S.H., W.K.C.), Department of Medicine (H.-J.S.H., W.K.C.), Center for Molecular Genetics (W.K.C.), and Cancer Center (W.K.C.), University of California San Diego, La Jolla, CA 92093-0660; Institute of Cell Biology, University of Essen Medical School, and West German Cancer Center, Hufelandstrasse 55, D45122 Essen, Germany (A.K.-R); and Department of Anatomy and Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond VA 23298-0709 (O.B., V.W.S., R.Y.)
2 Address correspondence and reprint requests to Oliver Bögler, Ph.D., Departments of Anatomy and Neurosurgery, Virginia Commonwealth University, PO Box 980709, Richmond, VA 23298-0709.
Abstract
Differential display poymerase chain reaction analysis was used to compare five differentiation states of the O-2A progenitor-like cell line CG4: progenitor cells and cells at 12 h or 4 days after the induction of differentiation into oligodendrocytes or astrocytes. This led to the identification of 52 sequence tags that were expressed differentially with cellular phenotype. One sequence was upregulated during differentiation of CG4 cells and represented a novel gene that we named SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes). This gene encodes an SH3 domain-containing adapter protein with sequence similarity to the CD2AP (CD2 adapter protein) and CMS (Cas ligand with multiple Src homology) genes. SETA mRNA was expressed at high levels in the developing rat brain but was barely detectable in the normal adult rat or human brain. However, SETA mRNA was found in approximately one half of the human gliomas tested, including astrocytomas grades II, III, and IV, as well as oligodendrogliomas, mixed oligoastrocytomas, and human glioma-derived cell lines. A rat glioma generated by treatment with the alkylating carcinogen ethylnitrosourea on postnatal day 1 and a derived cell line also expressed SETA mRNA. Furthermore, in an in vitro model of astrocytoma progression based on p53-/- astrocytes, expression of SETA was restricted to cells that are tumorigenic.
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