The long range purpose of this project is to investigate the roles of cellular oncogenes and retroviruses in neoplasia, and to gain insight in the mechanisms of gene regulation associated with cell differentiation and neoplasia. The topics of current interest are: 1) The role of proto-oncogenes and endogenous provirus loci in the oncogenesis of spontaneous reticulum cell neoplasms (RCN) of SJL/J mice. We found a high incidence of rearrangements not only in the c-abl but also in the endogenous ecotropic provirus loci in these tumors. The results are consistent with the hypothesis that activation of c-abl by promotor/enhancer insertion involving endogenous ecotropic proviruses may play a role in some RCN oncogenesis in SJL/J mice. 2) The role of mos in the anchorage-independent (AI) growth and metastatic ability of S+L- mink cells superinfected with a novel dual-tropic retrovirus (E1BX-MuLV). A marked amplification and rearrangement of v-mos in the chromosomal DNA accompanied by an increased number of E1BX-MuLV proviruses integrated near v-mos loci, and an enhanced expression of v-mos mRNA were correlated with the AI phenotype, oncogenicity, and metastatic potential of S+L- mink cells superinfected with the E1BX-MuLV. 3) Oncogene amplification, rearrangement and expression in human embryonal carcinomas (EC), and choriocarcinomas. Two cell lines of human EC, Tera-1 and Tera-2, showed an enhanced Ki-ras mRNA expression as well as an amplification and rearrangement of Ki-ras-2 gene. NIH/3T3 cells transfected with the Tera-2 DNA produced tumors in nude mice, and secondary and tertiary transfectants proved to be tumorigenic. Identification of the activated oncogene is in progress. 4) Monoclonal antibodies against HTLV-I. Among many hybridomas that were positive in the initial screening, two have been shown to produce monoclonal antibodies against 69 kd viral protein.
