Induction of HOX-2 genes in P19 embryocarcinoma cells is dependent on retinoic acid receptor alpha.

In vertebrate embryos retinoic acid can act as a teratogen and may have a natural function as a morphogen. In both cases the mechanism by which retinoic acid exerts its effect may involve alteration of the level of HOX gene transcription. We have investigated the role of retinoic acid receptor alpha (RAR alpha) in retinoic acid-dependent induction of HOX-2 gene expression in embryocarcinoma (EC) cells by using the P19 RAC65 EC cell line, which is retinoic acid-resistant due to the expression of a dominant negative RAR alpha. No induction of HOX-2 genes by retinoic acid was seen, while in P19 RAC65 EC cells stably transfected with human RAR alpha under the control of a constitutive promoter HOX-2 gene induction is restored. This shows that RAR alpha is involved in HOX gene induction by retinoic acid.