AVIAN MYELOBLASTIC CELL-LINES TRANSFORMED BY 2 NUCLEAR ONCOPROTEINS, P135(GAG-MYB-ETS) AND P61 63(MYC) - A MODEL OF RETINOIC ACID-INDUCED DIFFERENTIATION NOT ABROGATED BY V-ERBA/

We previously demonstrated that the retroviral construct MHE226 transd ucing both the P135gag-myb-ets and p61/63myc nuclear proteins induces solid hemopoietic tumors in early chicken embryos. In the present pape r, we report the characterization of two MHE226-transformed cell lines established from such hemopoietic tumors retrieved from the heart of a 13-day embryo. Cytological analysis indicated a myeloblastic phenoty pe. These MHE226 cell lines were positive for the MEP17 monoclonal ant ibody but were negative for the myeloblast-specific 51/2 monoclonal an tibody. MHE226 cell lines displayed a doubling time of about 20-24 h a nd were maintained for at least 1 year. Contrary to E26 myeloblastic c ell lines, MHE226 cell lines were independent of chicken myelomonocyti c growth factor and could be maintained in serum-free medium. MHE226 c ell lines could be induced to differentiate toward the monocytic linea ge by retinoic acid. Retinoic acid inhibited proliferation of MHE226 c ell lines as early as day 1. After 3 days, MHE226 cells displayed cyto logical, enzymatic (a-naphthyl acetate esterase and chloroacetate este rase), and functional (phagocytosis) characteristics of monocytic cell s. The retinoic acid-induced differentiation of MHE226 cells could not be inhibited by v-erbA. Thus, MHE226-transformed cell lines represent a novel model of cell transformation by two nuclear oncoproteins. Fur thermore, they provide a model to study molecular mechanisms implicate d in the monocytic differentiation program.