v-erbA acts on retinoic acid receptors in immature avian erythroid cells

Abstract

The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes an aberrant version of a gene for a thyroid hormone receptor (c-erbA) and functions in neoplasia by blocking erythroid differentiation and altering the growth properties of fibroblasts. The v-erbA gene has been proposed to act as a dominant negative allele, functioning by interfering with the actions of its normal cell homologs, the thyroid hormone receptors. The v-erbA protein can also, however, interfere with the actions of other members of the nuclear hormone receptor family, and it has been proposed that interference with a retinoic acid-mediated response may be a crucial determinant of v-erbA's function in the cancer cell. Here we report that the ability of v-erbA to interfere with retinoic acid receptor (RAR) action extends to the neoplastic erythroid cell and that v-erbA can inhibit transcriptional activation by all three isoforms (alpha, beta, and gamma) of RAR. Overexpression of RAR-alpha was found to partially overcome the presumptive v-erbA block to transcription in the erythroleukemic cell. These results are consistent with our hypothesis that v-erbA can act in neoplasia by interfering with a retinoic acid-mediated signal transduction pathway.