c-erbB activation in avian leukosis virus-induced erythroblastosis: clustered integration sites and the arrangement of provirus in the c-erbB alleles

禽白血病病毒诱导的成红细胞增多症中 c-erbB 的激活:c-erbB 等位基因中聚集的整合位点和前病毒的排列

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Abstract

There is considerable evidence that links the activation of cellular genes to oncogenesis. We previously reported that structural rearrangements in the cellular oncogene c-erbB correlate with the development of erythroblastosis induced by avian leukosis virus (ALV). c-erbB recently has been shown to be related to the gene encoding epidermal growth factor receptor. We now have characterized the detailed mechanisms of c-erbB activation by ALV proviruses. We report here that the ALV proviral integration sites are clustered 5' to the region where homology to v-erbB starts, suggesting that interruption in this region of c-erbB is important for its activation. The proviruses are oriented in the same transcriptional direction as c-erbB and usually are full-size. The latter finding is in contrast to the frequent deletions observed within the c-myc-linked proviruses in B-cell lymphomas. We have also identified a second c-erbB allele, which differs from the previously known allele primarily by a deletion in an intron region. This allele is also oncogenic upon mutation by an ALV provirus.

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