The nuclear-associated endoplasmic reticulum is an early target for the action of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate in C3H/10T1/2 fibroblasts.

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) had a dual effect on the cellular membranes of C3H/10T1/2 cells in that it caused both a stimulation of [3H]choline incorporation and an enhancement of the solubilization of choline from prelabelled cells. Subfractionation studies showed that the release of [3H]choline occurred almost exclusively from nuclear-associated endoplasmic reticulum. The release was dependent on the presence of Mg2+ and Ca2+, indicating an enzyme-mediated reaction. In vivo, TPA stimulated the incorporation of [3H]choline into all subcellular fractions. The data indicate that the nuclear-associated endoplasmic reticulum represents an early target for TPA action.