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

Publication Type	Academic Article
Authors	Nakamura H, Yoshimura K, Bajocchi G, Trapnell B, Pavirani A, Crystal R
Journal	FEBS Lett
Volume	314
Issue	3
Pagination	366-70
Date Published	12/21/1992
ISSN	0014-5793
Keywords	Cystic Fibrosis, Gene Expression Regulation, Membrane Proteins, Tumor Necrosis Factor-alpha
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-alpha (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 posttranscriptional level.
DOI	10.1016/0014-5793(92)81507-i
PubMed ID	1281791