Antisense oligonucleotides to human lipocortin-1 inhibit glucocorticoid-induced inhibition of A549 cell growth and eicosanoid release.
Glucocorticoids actively inhibit the growth of A549 cells by suppressing the release of factors such as prostaglandin E2 (PGE2) necessary for their proliferation. This effect is largely mediated through induction of the protein lipocortin-1. We now show that transient transfection of A549 cells with an antisense DNA oligonucleotide targeted to a region coding the unique N-terminal portion of human lipocortin-1 blocks the induction of lipocortin-1 protein following glucocorticoid treatment and completely reverses glucocorticoid-induced suppression of cell proliferation and PGE2 release. A scrambled oligonucleotide was without effect. Continued culture of A549 cells in the presence of this oligonucleotide results in a sustained increase in cell proliferation and PGE2 release. This study reinforces the importance of lipocortin-1 as a negative modulator of cell growth and eicosanoid generation in this system.
Department of Biochemical Pharmacology, William Harvey Institute, Medical College of St Bartholomew's Hospital, London, U.K.
J D
JD
Croxtall
R J
RJ
Flower
D017305:Annexin A1 / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis*; D015870:Gene Expression; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000494:pharmacology*
D017305:Annexin A1; D015777:Eicosanoids; D005938:Glucocorticoids; D016376:Oligonucleotides, Antisense; D003907:Dexamethasone; D015232:Dinoprostone