INDUCTION OF PLATELET-DERIVED GROWTH-FACTOR B C-SIS BY THE V-ERBA ONCOGENE IN GLIAL-CELLS/

The v-erbA oncogene codes for a mutated form of the thyroid hormone re ceptor TRlc-eubA-alpha, Thyroid hormone (triiodothyronine, T3) regulat es glial functions such as myelination and both astrocytes and oligode ndrocytes have been shown to express thyroid hormone receptors (TRs). To study putative effects of v-erbA on glial precursors, we have expre ssed it in a glial clonal cell line established from early embryonal m ouse brain, We have found that v-erbA increases cell survival in serum -free conditions. Moreover, v-erbA-expressing cells show a substantial growth in the presence of insulin or IGF-I, whereas normal and TR/c-e rbA-over-expressing cells progressively degenerate. By Northern blotti ng, immuno-fluorescence, immunoprecipitation, and neutralization exper iments, we show that v-erbA actions are mediated by an increase in the levels of PDGF B/c-sis mRNA and protein. We used anti-PDGF receptor a nd antiphosphotyrosine antibodies to show the constitutive activation of PDGF receptors in B3.1+v-erbA cells, and neutralizing anti-PDGF ant ibodies to demonstrate that v-erbA enhances the secretion of active PD GF into the culture medium. Our data indicate that v-erbA induces PDGF B/c-sis, a factor involved in the generation df gliomas, the most com mon central nervous system tumor in humans.