Transcriptional and post-transcriptional mechanisms for lysophosphatidic acid-induced cyclooxygenase-2 expression in ovarian cancer cells

摘要: Emerging evidence suggests that lysophosphatidic acid (LPA) is a physiological regulator of cyclooxygenase-2 (Cox-2) expression. Herein we used ovarian cancer cells as model to investigate the molecular mechanisms link LPA G protein-coupled receptors (GPCRs) Cox-2 stimulated expression and release prostaglandins though LPA1, LPA2, LPA5 receptors. The effect involves both transcriptional activation post-transcriptional enhancement mRNA stability. consensus sites for C/EBP in promoter were essential by LPA. NF-κB AP-1 transcription factors commonly involved inducible dispensable. Dominant-negative C/EPBβ inhibited Furthermore, C/EBPβ phosphorylation activity through novel mechanism integrating GPCR signals permissive from receptor tyrosine kinase (RTK). This role RTK was not consistent with transactivation RTK, full RTKs their own agonists only weakly C/EBP. In addition activation, RNA stabilization protein HuR bound protected LPA-stimulated cells, indicating an active sustaining induction during responses.—Oyesanya, R. A., Lee, Z. P., Wu, J., Chen, Song, Y., Mukherjee, Dent, Kordula, T., Zhou, H., Fang, X. Transcriptional acid-induced cells.