The targeted disruption of both alleles of RAR beta(2) in F9 cells resultsin the loss of retinoic acid-associated growth arrest

F9 teratocarcinoma cell lines, carrying one or two disrupted alleles of the RAR beta(2) gene, were generated by homologous recombination to study the role of RAR beta(2) in mediating the effects of retinoids on cell growth an d differentiation. Retinoic acid (RA) does not induce growth arrest of the RAR beta(2)-/- cells, whereas the F9 WT and RAR beta(2)+/- heterozygote lin es undergo RA-induced growth arrest. The RAR beta(2)+/- lines also exhibit a faster cell cycle transit time in the absence of RA. The RAR beta(2)-/- s tem cells exhibit an altered morphology when compared with the F9 WT parent line, and after RA treatment, the RAR beta(2)-/- cells do not exhibit a fu lly differentiated cell morphology, As compared with F9 WT cells, the RAR b eta-/- cells exhibited a markedly lower induction of several early RA-respo nsive genes and no induction of laminin B1, a late response gene. The induc tion of RA metabolism in the F9 RAR beta(2)-/- cells following differentiat ion was not impaired. The research presented here, and prior research sugge st that RAR beta is required for RA-induced growth arrest in a variety of c ell types and that RAR beta also functions in mediating late responses to R A. These findings are significant in view of the reduced expression of RAR beta transcripts in a number of different types of human carcinomas.