Abstract
Glucocorticoids actively inhibit the growth of A549 cells by suppressing the release of factors such as prostaglandin E 2 (PGE 2) 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 PGE 2 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 PGE 2 release. This study reinforces the importance of lipocortin-1 as a negative modulator of cell growth and eicosanoid generation in this system.
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