Elevated prostaglandin H synthase gene expression in ras-transformed cells

1. rPDGF stimulates PGE2 release in wild type, but not ras transformed NIH-3T3 cells. 2. Ras transformation blocks PGE2 release by inhibiting phospholipase C activation, IP3 synthesis, and Ca2+ mobilization. 3. rPDGF stimulation of wild type NIH-3T3 cells increases both prostaglandin H synthase (PGHS) mRNA levels and PGHS enzyme levels as measured by immunoblot. However, PGHS gene transcription is not required for PDGF-stimulated PGE2 release. 4. Ras transformed NIH-3T3 cells display elevated basal PGE2 synthesis, and very high levels of both PGHS mRNA and enzyme. rPDGF does not further stimulate PGHS gene transcription. 5. Exogenous PGE2 attenuates rPDGF-stimulated cell proliferation in both wild type and ras transformed cells. 6. These data suggest that increased PGHS gene expression and enhanced basal PGE2 synthesis may be in response to the unregulated growth of ras transformed cells.