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Tumor necrosis factor modulation of expression of the cystic fibrosis transmembrane conductance regulator gene
Author(s) -
Nakamura Hidenori,
Yoshimura Kunihiko,
Bajocchi Gianluigi,
Trapnell Bruce C.,
Pavirani Andrea,
Crystal Ronald G.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81507-i
Subject(s) - cystic fibrosis transmembrane conductance regulator , gene expression , tumor necrosis factor alpha , biology , microbiology and biotechnology , messenger rna , gene , cystic fibrosis , transcriptional regulation , promoter , regulation of gene expression , transmembrane protein , transcription factor , cancer research , endocrinology , genetics , receptor
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.