Down-regulation of cystic fibrosis gene mRNA transcript levels and induction of the cystic fibrosis chloride secretory phenotype in epithelial cells by phorbol ester

B. C. Trapnell, P. L. Zeitlin, C. S. Chu, K. Yoshimura, H. Nakamura, W. B. Guggino, J. Bargon, T. C. Banks, W. Dalemans, A. Pavirani, J. P. Lecocq, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)10319-10323
Number of pages5
JournalJournal of Biological Chemistry
Volume266
Issue number16
Publication statusPublished - 16 Aug 1991
Externally publishedYes

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Phorbol Esters
Tetradecanoylphorbol Acetate
Cystic Fibrosis
Chlorides
Down-Regulation
Genes
Epithelial Cells
Phenotype
Messenger RNA
Colforsin
Ion Transport
Cells
Ions
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Down-regulation of cystic fibrosis gene mRNA transcript levels and induction of the cystic fibrosis chloride secretory phenotype in epithelial cells by phorbol ester. / 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.; Lecocq, J. P.; Crystal, Ronald.

In: Journal of Biological Chemistry, Vol. 266, No. 16, 16.08.1991, p. 10319-10323.

Research output: Contribution to journalArticle

Trapnell, BC, Zeitlin, PL, Chu, CS, Yoshimura, K, Nakamura, H, Guggino, WB, Bargon, J, Banks, TC, Dalemans, W, Pavirani, A, Lecocq, JP & Crystal, R 1991, 'Down-regulation of cystic fibrosis gene mRNA transcript levels and induction of the cystic fibrosis chloride secretory phenotype in epithelial cells by phorbol ester', Journal of Biological Chemistry, vol. 266, no. 16, pp. 10319-10323.
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. ; Lecocq, J. P. ; Crystal, Ronald. / Down-regulation of cystic fibrosis gene mRNA transcript levels and induction of the cystic fibrosis chloride secretory phenotype in epithelial cells by phorbol ester. In: Journal of Biological Chemistry. 1991 ; Vol. 266, No. 16. pp. 10319-10323.
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abstract = "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.",
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