Trapnell B C, Zeitlin P L, Chu C S, Yoshimura K, Nakamura H, Guggino W B, Bargon J, Banks T C, Dalemans W, Pavirani A
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1991 Jun 5;266(16):10319-23.
To evaluate the hypothesis that phorbol myristate acetate (PMA) might modulate the expression of the cystic fibrosis (CF) gene in epithelial cells, we examined the effect of PMA on CF mRNA levels and regulation of Cl- secretion. Strikingly, PMA down-regulated CF mRNA transcript numbers in a dose- and time-dependent manner. Importantly, in parallel with the reduction of CF mRNA levels, PMA-treated cells were unable to up-regulate Cl- secretion in a normal fashion in response to forskolin, an effect which was also dose- and time-dependent. Thus, PMA is capable of modulating expression of the CF gene and induces T84 cells to adopt the "CF phenotype" in regard to regulation of Cl- ion transport.
