OVEREXPRESSION OF C-TERMINALLY BUT NOT N-TERMINALLY TRUNCATED MYB INDUCES FIBROSARCOMAS - A NOVEL NONHEMATOPOIETIC TARGET-CELL FOR THE MYB ONCOGENE

The myb oncogene encodes a DNA-binding transcriptional transactivator which can become a hematopoietic cell-transforming protein following t he deletion of amino acid sequences from either its amino or carboxyl terminus. Although a number of hematopoietic tumors express terminally deleted variants of Myb, the involvement of truncated Myb in nonhemat opoietic tumors has not been adequately investigated. To assess the fu ll spectrum of Myb's oncogenic capability, a replication-competent ret roviral vector (RCAMV) was used to express a full-length protein (C-My b), an amino-terminally truncated protein (VCC- or DELTAN-Myb), a carb oxyl-terminally truncated protein (T-Myb), or a doubly truncated prote in (VCT-Myb) in vivo. These viruses were injected intravenously into 1 0-day chicken embryos, and the infected chicks were monitored for tumo rs. Approximately 4 to 8 weeks after hatching, the majority (30 of 39 [77%]) of animals infected with the T-Myb retrovirus (without 214 carb oxyl-terminal residues) developed nodular muscle tumors which could be identified by both morphologic and immunohistochemical criteria as fi brosarcomas. Identically appearing tumors could also be found in the k idney of some T-Myb-infected animals. The T-Myb-induced fibrosarcomas expressed the appropriately sized T-Myb protein, contained an unaltere d proviral T-myb gene, and showed clonal proviral integration sites. I n comparison, no sarcomas were observed in any of the animals infected with the amino-terminally truncated (VCC- and DELTAN-Myb) or doubly t runcated (VCT-Myb) viruses. A loss of carboxyl-terminal but not amino- terminal sequences can thus convert Myb into a potent in vivo transfor ming protein for nonhematopoietic mesenchymal cells. In comparison, a truncation of either or both ends of the protein can activate Myb into a hematopoietic cell-transforming protein.