A hepatitis B virus pre-S-retinoic acid receptor beta chimera transforms erythrocytic progenitor cells in vitro.
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.
Garcia
M
M
Ecole Normale Supérieure de Lyon, Laboratoire de Biologie Moléculaire et Cellulaire, Institut National de la Recherche Agronomique, France.
de Thé
H
H
Tiollais
P
P
Samarut
J
J
Dejean
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells; D002256:Carbonic Anhydrases / Q000096:biosynthesis / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D002645:Chickens; D004794:Enzyme Repression; D004912:Erythrocytes / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000097:blood; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D018774:Oncogene Proteins v-erbA; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D015183:Restriction Mapping; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D007527:Isoenzymes; D018774:Oncogene Proteins v-erbA; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; D011505:Protein-Tyrosine Kinases; D002256:Carbonic Anhydrases