Abstract
The JB-6 mouse epidermal cell line has been used as a model system for studying the mechanism of late-stage promoter-dependent preneoplastic progression. The studies reported here are concerned with determining whether there is a requirement for mitogenic stimulation in promotion of anchorage independence and tumorigenicity in JB-6 cells. Such a requirement would predict that variants selected for 12-O-tetradecanoylphorbol 13-acetate (TPA) mitogen resistance would also be promotion resistant. Promotion-responsive cell lines have been selected for resistance to TPA-induced mitogenic stimulation at plateau density by cotreatment with colchicine and removal of mitogen-responsive colchicine-detached cells. The selected TPA-resistant population of cells showed a mitogenic response that was diminished by a factor of four but showed no diminution in the promotion-of-anchorage-independence response to TPA. Mitogen-resistant clonal lines derived from the selected population fell into three phenotypic classes when assayed in soft agar: (i) anchorage-independent transformants; (ii) variants resistant to promotion of anchorage independence by TPA; and (iii) variants sensitive to promotion by TPA. The existence of the latter class (i.e., the mitogen-resistant promotable variants) indicates a lack of obligatory causal relationship between TPa-induced mitogenesis and late-stage promotion and, thereby suggests that the two events can be dissociated.
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Selected References
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