Abstract
In this report, we investigated the transforming properties of retinoic acid receptor beta (RAR beta). The v-erbA protein, which is the viral oncogenic homologue of the thyroid hormone receptor, was replaced by either the complete RAR beta (beta R) or a hepatitis B virus pre-S-RAR beta (H beta R) hybrid product in an avian erythroblastosis virus-based vector. In chicken hematopoietic cells, the H beta R protein was able to transform erythroid progenitor cells, whereas no such transformation was observed with the wild-type beta R protein. Moreover, the fully transformed phenotype was observed even in the absence of v-erbB, and H beta R-transformed erythroid cells grew independently of growth factors and transforming growth factor alpha. The analysis of erythrocytic-specific proteins revealed that the transformed cells were blocked at the colony-forming unit-erythroid stage and that the expression of the carbonic anhydrase II gene, a gene normally regulated by thyroid hormones, was repressed by the H beta R protein. Finally, hepatocarcinomas rapidly developed in some chickens infected in ovo with viruses encoding either the normal or the hybrid H beta R, suggesting that an inappropriate expression of the RAR beta gene may represent an important event in oncogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Bone Marrow Cells
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Carbonic Anhydrases / biosynthesis
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Carbonic Anhydrases / blood
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Carrier Proteins / genetics
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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Cell Division
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Cell Line, Transformed
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Cell Transformation, Neoplastic*
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Chick Embryo
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Chickens
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Enzyme Repression
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Erythrocytes / physiology*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / physiology*
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Hepatitis B virus / genetics*
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Humans
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Isoenzymes / biosynthesis
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Isoenzymes / blood
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Liver Neoplasms / genetics
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Liver Neoplasms / pathology
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Liver Neoplasms, Experimental / genetics
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Liver Neoplasms, Experimental / pathology
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Molecular Sequence Data
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Oncogene Proteins v-erbA
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Oncogenes*
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Protein-Tyrosine Kinases / genetics*
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Receptors, Retinoic Acid
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Recombinant Fusion Proteins / isolation & purification
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Recombinant Fusion Proteins / metabolism
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Restriction Mapping
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Retroviridae Proteins, Oncogenic / genetics
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Retroviridae Proteins, Oncogenic / isolation & purification
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Retroviridae Proteins, Oncogenic / metabolism*
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism*
Substances
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Carrier Proteins
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Isoenzymes
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Oncogene Proteins v-erbA
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Receptors, Retinoic Acid
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Recombinant Fusion Proteins
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Retroviridae Proteins, Oncogenic
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Viral Envelope Proteins
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Protein-Tyrosine Kinases
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Carbonic Anhydrases