Abstract
Lysophosphatidic acid (LPA; 1-acyl-2-hydroxy-sn-glycero-3-phosphate) is a lipid growth factor that stimulates the proliferation of ovarian cancer cells. Recent studies indicate that elevation of cellular cAMP levels inhibits ovarian epithelial cancer cell growth. In this study, we investigated the effects of elevating cellular cAMP levels on LPA stimulation of OVCAR-3 ovarian cancer cell growth and on LPA stimulation of the serum response factor (SRF) transcription factor. Treatment of OVCAR-3 cells with forskolin and isobutylmethylxanthine (IBMX; 3-Isobutyl-1-methylxanthine) inhibited LPA stimulation of growth. LPA stimulation of SRF-mediated transcription was also inhibited in OVCAR-3 cells that were incubated with forskolin, dibutyryl cyclic AMP (db-cAMP), or paired cAMP analogues (N(6)-mono-tert-butylcarbamoyladenosine-3', 5'-cyclic monophosphate [6-MBC-cAMP] and Sp-5,6-DCl-BIMPS), which selectively activate type II protein kinase A. In contrast, incubation with a cAMP analogue (8-(4-chloro-phenylthio)-2'-O-methyadenosine-3',5'-cyclic monophosphate [8CPT-2Me-cAMP]) that specifically activates the cAMP inducible Rap1 exchange factor, Epac, did not inhibit SRF. Similar results were obtained when HepG2 hepatoma cells, which do...Continue Reading
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