Tumor necrosis factor modulation of expression of the cystic fibrosis transmembrane conductance regulator gene

Hidenori Nakamura, Kunihiko Yoshimura, Gianluigi Bajocchi, Bruce C. Trapnell, Andrea Pavirani, Ronald Crystal

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Based on the knowledge that expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be modulated at the transcriptional level, and that the CFTR gene promoter contains sequences homologous to elements in other promoters that respond to tumor necrosis factor-α (TNF), we evaluated the hypothesis that TNF might modulate CFTR gene expression in epithelial cells. Studies with HT-29 cells, a colon epithelium-derived tumor cell line known to express the CFTR gene, demonstrated that TNF downregulated CFTR mRNA transcript levels in a dose- and time-dependent fashion. Interestingly, nuclear run-on analyses demonstrated that TNF did not affect the rate of transcription of CFTR gene, but exposure of the cells to TNF did modify the stability of CFTR mRNA transcripts, resulting in a mRNA half-life that was reduced to 65% of the resting level. These observations suggest that CFTR gene expression can be modulated by TNF, at least in part, at the post-transcriptional level.

Original languageEnglish
Pages (from-to)366-370
Number of pages5
JournalFEBS Letters
Volume314
Issue number3
DOIs
Publication statusPublished - 21 Dec 1992
Externally publishedYes

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Keywords

  • Cystic fibrosis transmembrane conductance regulator, Gene expression
  • mRNA stability
  • mRNA transcript
  • Transcription
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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