F9 embryonal carcinoma cells treated with 1 µm 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.

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