© 2000 by Society
© 2000 by the Society forNeuro-Oncology
SETA: A novel SH3 domain-containing adapter molecule associatedwith malignancy in astrocytes
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 CaliforniaSan Diego, La Jolla, CA 92093-0660; Institute of CellBiology, 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, MedicalCollege 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, POBox 980709, Richmond, VA 23298-0709.
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Abstract |
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Differential display poymerase chain reaction analysis was used to comparefive differentiation states of the O-2A progenitor-like cell line CG4:progenitor cells and cells at 12 h or 4 days after the induction ofdifferentiation into oligodendrocytes or astrocytes. This led to theidentification of 52 sequence tags that were expressed differentially withcellular phenotype. One sequence was upregulated during differentiation of CG4cells and represented a novel gene that we named SETA (SH3domain-containing gene expressed in tumorigenic astrocytes). This gene encodesan SH3 domain-containing adapter protein with sequence similarity to theCD2AP (CD2 adapter protein) and CMS (Cas ligand withmultiple Src homology) genes. SETA mRNA was expressed at high levelsin the developing rat brain but was barely detectable in the normal adult rator human brain. However, SETA mRNA was found in approximately one half of thehuman gliomas tested, including astrocytomas grades II, III, and IV, as wellas oligodendrogliomas, mixed oligoastrocytomas, and human glioma-derived celllines. A rat glioma generated by treatment with the alkylating carcinogenethylnitrosourea on postnatal day 1 and a derived cell line also expressedSETA mRNA. Furthermore, in an in vitro model of astrocytoma progression basedon p53-/- astrocytes, expression of SETA was restricted tocells that are tumorigenic.
Received July 7, 1999; Accepted August 31, 1999
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