A variant F9 embryonal carcinoma cell line which undergoes incomplete differentiation in retinoic acid.

F9 embryonal carcinoma cells treated with 1 microM retinoic acid undergo irreversible differentiation and simultaneously lose their tumorigenicity. Described here are the isolation and characterization of an F9 variant clone (5C), which undergoes partial differentiation in retinoic acid. The behavior of 5C cells indicates that retinoic acid successfully initiates the differentiation pathway but that complete differentiation is not achieved due to a subsequent block in the pathway. The fact that 5C cells do not undergo complete differentiation, or lose their tumorigenicity in response to retinoic acid, indicates that the lesion affects an element involved in the regulation of both these events. Therefore, further genetic and biochemical characterization of this variant should provide information concerning the relationship between the regulation of differentiation and tumorigenicity. Furthermore, the isolation of this variant establishes the feasibility of genetically dissecting the various steps of the differentiation pathway.

Differentiation of F9 embryonal carcinoma cells. Differences in the effects of retinoic acid, 5-bromodeoxyuridine, and N'-N'-dimethylacetamide.

We found that monolayer cultures of F9 cells induced to differentiate with trans-retinoic acid (RA) contain two major subpopulations of cells. These two cell types can be distinguished by their cellular morphology, their pattern of laminin accumulation, and their ability to undergo further differentiation in response to N6-O2-dibutyryl adenosine 3':5' cyclic monophosphoric acid (dBcAMP). Furthermore, the developmental pathway induced by RA appears to lead to two alternative pathways, and differentiation at the branch point is either directly or indirectly controlled by cAMP. Differentiation along one branch of this pathway can be induced by 5-bromodeoxyuridine, whereas differentiation along an unrelated pathway is induced by N'-N'-dimethylacetamide. In all cases, differentiation is closely paralleled by suppression of the tumorigenic phenotype, indicating that these two processes are tightly linked and probably share a common step.