v-rel Induces ectopic expression of an adhesion molecule, DM-GRASP, during B-lymphoma development.
In an effort to identify aberrantly expressed genes in v-rel-induced tumors, monoclonal antibodies were developed that reacted selectively with avian B-cell tumors. One antibody, HY78, immunoprecipitated a 120-kDa glycoprotein (p120) from cells that express v-rel. N-terminal amino acid sequencing of p120 identified a 27-amino-acid sequence that is also present in DM-GRASP, an adhesion molecule belonging to the immunoglobulin superfamily. Evidence from tissue distribution, immunological cross-reaction, PCR amplification, cDNA cloning, and DNA sequence shows that p120 is indeed DM-GRASP. Northern (RNA) analysis using a probe from the DM-GRASP gene identified a 5.3-kb transcript in mRNA from bursa, thymus, and brain as well as from v-rel-induced B-cell lymphomas but not from bursal B cells. The induction of this protein by v-rel during the development of bursal B-cell lymphomas appears, therefore, to be ectopic in nature. Overexpression of v-rel or c-rel in chicken embryonic fibroblasts, B-cell lines, and spleen mononuclear cells induces the expression of DM-GRASP. The ratio of DM-GRASP to v-Rel was fivefold higher than that of DM-GRASP/c-Rel in a B-cell line, DT95. Interestingly, the presence of HY78 antibody inhibits the in vitro proliferation of v-rel-transformed cells but not cells that immortalized by myc. These data suggest that DM-GRASP is one of the genes induced during v-rel-mediated tumor development and that DM-GRASP may be involved in the growth of v-rel tumor cells.
Zhang
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Mary Babb Randolph Cancer Center, West Virginia University, Morgantown 26506-9177.
Slaughter
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Humphries
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EH
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000276:immunology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000302:isolation & purification; D002460:Cell Line; D002642:Chick Embryo; D017931:DNA Primers; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D015723:Gene Library; D006023:Glycoproteins / Q000096:biosynthesis / Q000302:isolation & purification; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D009857:Oncogenes; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D020410:Activated-Leukocyte Cell Adhesion Molecule; D000906:Antibodies; D000911:Antibodies, Monoclonal; D015816:Cell Adhesion Molecules, Neuronal; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger