Retroviral insertional activation of the c-myb proto-oncogene in a Marek's disease T-lymphoma cell line.
Marek's disease virus (MDV) is an avian herpesvirus that causes, in chickens, a lymphoproliferative disease characterized by malignant transformation of T lymphocytes. The rapid onset of polyclonal tumors indicates the existence of MDV-encoded oncogenic products. However, the molecular basis of MDV-induced lymphoproliferative disease and latency remains largely unclear. Several lines of evidence suggest that MDV and Rous-associated virus (RAV) might cooperate in the development of B-cell lymphomas induced by RAV. Our present results indicate for the first time that MDV and RAV might also act synergistically in the development of T-cell lymphomas. We report an example of an MDV-transformed T-lymphoblastoid cell line (T9) expressing high levels of a truncated C-MYB protein as a result of RAV integration within one c-myb allele. The chimeric RAV-c-myb mRNA species initiated in the 5' long terminal repeat of RAV are deprived of sequences corresponding to c-myb exons 1 to 3. The attenuation of MDV oncogenicity has been strongly related to structural changes in the MDV BamHI-D and BamHI-H DNA fragments. We have established that both DNA restriction fragments are rearranged in the T9 MDV-transformed cells. Our results suggest that retroviral insertional activation of the c-myb proto-oncogene is a critical factor involved in the maintenance of the transformed phenotype and the tumorigenic potential of this T-lymphoma cell line.
Laboratoire d'Oncologie Virale et Moléculaire, UMR CNRS 146, Institut Curie, Centre Universitaire, Orsay, France.
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E
Le Rouzic
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B
Perbal
D000483:Alleles; D001354:Avian Leukosis Virus / Q000235:genetics*; D004279:DNA, Viral / Q000032:analysis; D015245:Deoxyribonuclease BamHI / Q000378:metabolism; D015870:Gene Expression; D015321:Gene Rearrangement; D008381:Herpesvirus 2, Gallid / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016662:Virus Integration
D004279:DNA, Viral; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D015534:Trans-Activators; D015245:Deoxyribonuclease BamHI