Induction of anchorage-independent growth of mouse JB6 cells by cholera toxin

Cholera toxin (CT) at concentrations of 0.1-100 ng/ml induced anchorage-independent growth and DNA synthesis of JB6 cells derived from mouse epidermis. This induction was reversible. CT caused marked increase in the level of intracellular cAMP. Forskolin also increased the cAMP level and induced anchorage-independent growth. However, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] induced irreversibly anchorage-independent growth of JB6 cells but did not increase the cAMP level. TPA-resistant clone-30 cells were also resistant to CT in terms of anchorage-independent growth and cAMP induction. Retinoic acid inhibited the induction of anchorage-independent growth of JB6 cells by CT, TPA and 1 alpha,25(OH)2D3. These results suggest that anchorage-independent growth of JB6 cells is induced by cAMP-dependent and cAMP-independent pathways, both of which may include a retinoic acid-sensitive step.