Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells

Russell R. Hoover, Klaus H. Thomas, Joanna Floros

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Glucocorticoids have complex effects on human surfactant protein (SP) SP-A1 and SP-A2 gene expression that occur at both transcriptional and post-transcriptional levels. In the lung adenocarcinoma cell line NCI-H441, dexamethasone causes a dose-dependent decrease in total SP-A mRNA levels and inhibits SP-A gene transcription. In this study, a deletional analysis of the SP-A1 promoter was performed in order to identify cis-acting elements that mediate dexamethasone responsiveness in NCI-H441 cells. The region -32/+63 relative to the start of SP-A1 transcription mediated both basal promoter activity and dexamethasone repression of transcription. Removal of the region +18/+63 abolished dexamethasone responsiveness, indicating that sequences within this region are necessary for the inhibitory effect. Furthermore, the region -32/+63 formed a sequence-specific DNA-protein complex with NCI-H441 nuclear extract. This DNA-protein complex was induced by dexamethasone exposure and its formation was mediated partially by sequences within the region +26/+63.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalBiochemical Journal
Volume340
Issue number1
DOIs
StatePublished - May 15 1999

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Surface-Active Agents
Glucocorticoids
Dexamethasone
Transcription
Proteins
Pulmonary Surfactant-Associated Protein A
DNA
varespladib methyl
Gene expression
Genes
Cells
Gene Expression
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hoover, Russell R. ; Thomas, Klaus H. ; Floros, Joanna. / Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells. In: Biochemical Journal. 1999 ; Vol. 340, No. 1. pp. 69-76.
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Glucocorticoid inhibition of human SP-A1 promoter activity in NCI-H441 cells. / Hoover, Russell R.; Thomas, Klaus H.; Floros, Joanna.

In: Biochemical Journal, Vol. 340, No. 1, 15.05.1999, p. 69-76.

Research output: Contribution to journalArticle

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AB - Glucocorticoids have complex effects on human surfactant protein (SP) SP-A1 and SP-A2 gene expression that occur at both transcriptional and post-transcriptional levels. In the lung adenocarcinoma cell line NCI-H441, dexamethasone causes a dose-dependent decrease in total SP-A mRNA levels and inhibits SP-A gene transcription. In this study, a deletional analysis of the SP-A1 promoter was performed in order to identify cis-acting elements that mediate dexamethasone responsiveness in NCI-H441 cells. The region -32/+63 relative to the start of SP-A1 transcription mediated both basal promoter activity and dexamethasone repression of transcription. Removal of the region +18/+63 abolished dexamethasone responsiveness, indicating that sequences within this region are necessary for the inhibitory effect. Furthermore, the region -32/+63 formed a sequence-specific DNA-protein complex with NCI-H441 nuclear extract. This DNA-protein complex was induced by dexamethasone exposure and its formation was mediated partially by sequences within the region +26/+63.

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