IN-VIVO COOPERATION OF 2 NUCLEAR ONCOGENIC PROTEINS, P135(GAG-MYB-ETS) AND P61 63(MYC), LEADS TO TRANSFORMATION AND IMMORTALIZATION OF CHICKEN MYELOMONOCYTIC CELLS/

To investigate a possible in vivo cooperation between the p61/63(myc) and p135(gag-myb-ets) proteins, we used a previously constructed retro virus, named MHE226, which contains the fused v-myb and v-ets oncogene s of the E26 retrovirus and the v-myc oncogene of MH2. For that purpos e, chicken neuroretina cells producing MHE226 and pseudotyped with the Rous associated virus-1 (RAV-1) helper virus were injected in 1-day-o ld chickens. In control experiments, we also injected chicken neuroret ina cells producing E26 (RAV-1), RAV-1 alone, or constructs lacking on e of the oncogenes of MHE226. The average life span of MHE226-infected chickens is half that of E26-infected chickens. MHE226-infected chick ens harbor tumors scattered in many organs, but compared with E26, MHE 226 induced a weak leukemia. Study of integration sites suggests that the majority of the tumors results from clonal or oligoclonal events. Cell cultures were derived from the tumors of MHE226-infected chickens and grown in standard medium without addition of exogenous chicken my elomonocytic growth factor. These cells still divide at high rate afte r more than 100 passages and can thus be considered immortalized. By u sing several criteria, these cells were characterized as precursors of the myelomonocytic lineages.