SP-A 3'-UTR is involved in the glucocorticoid inhibition of human SP-A gene expression.
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.
Hoover
R R
RR
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Floros
J
J
D000483:Alleles; D001483:Base Sequence / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000037:antagonists & inhibitors; D003907:Dexamethasone / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008969:Molecular Sequence Data; D011510:Proteolipids / Q000037:antagonists & inhibitors / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020506:Untranslated Regions / Q000502:physiology*
D005938:Glucocorticoids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; C445842:SFTPA1 protein, human; C445843:SFTPA2 protein, human; D020506:Untranslated Regions; D013196:Dihydrotestosterone; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate; D006854:Hydrocortisone