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Departments of 1 Cellular and Molecular Physiology and 2 Pediatrics, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033
The synthetic
glucocorticoid dexamethasone has a major inhibitory effect on human
surfactant protein A1
(SP-A1) and
SP-A2 gene expression that occurs at
both the transcriptional and posttranscriptional levels. Toward the
identification of cis-acting elements
that may be involved in the dexamethasone regulation of SP-A mRNA
stability, chimeric chloramphenicol acetyltransferase (CAT) constructs
that contained various portions of SP-A1 or SP-A2 cDNA in place of the
native CAT 3'-untranslated region (UTR) were transiently
transfected into the lung adenocarcinoma cell line NCI-H441. CAT
activity was reduced in NCI-H441 cells by exposure to 100 nM
dexamethasone only for the chimeric CAT constructs that contained the
SP-A 3'-UTR. Moreover, the inhibitory response seen with
dexamethasone was greater for the 3'-UTR derived from the
SP-A1 allele
6A3 than with
the 3'-UTR derived from either the
SP-A1 allele
6A2 or
SP-A2 allele
1A0, indicating
differential regulation between SP-A
genes and/or alleles.
surfactant protein A; 3'-untranslated region; alleles; dexamethasone; messenger ribonucleic acid; transfection
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