Clonal analysis of the change in growth phenotype during embryonal carcinoma cell differentiation

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Abstract
Retinoic acid has been shown to induce the differentiation of mouse embryonal carcinoma cells. Previous workers have reported that bulk cultures of the differentiated derivatives have a slower growth rate and a reduced capacity to form tumours. We have analysed this change in growth rate for a sub-tetraploid EC cell line, PC 13 clone 5 MAz, at a clonal level and have shown that the production of cells with a slower growth rate is not a result of cell selection. We have also demonstrated that the action of retinoic acid on growth rate is delayed for approximately 48 h and that the new growth phenotype, once attained, is stable. Finally we have confirmed at a clonal level that the differentiated derivatives of EC cells exposed to retinoic acid have a reduced capacity to form tumours. Clones of EC cells exposed to retinoic acid for longer than 96 h are unable to form tumours in a 30-day period, whilst 87 % of their untreated counterparts are able to do so.