Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

Background: Factor VIIa (FVIIa) binding to tissue factor (TF) induces cell signaling via the protease activity of FVIIa and protease-activated receptor 2 (PAR2). Objective: We examined how the gene-expression profile induced by FVIIa corresponds to the profiles induced by protease-activated receptor I (PARI) or PAR2 agonists using MDA-MB-231 breast carcinoma cells that constitutively express TF, PARI and PAR2. Results and conelusions: Out of 8500 genes, FVIIa stimulation induced differential regulation of 39 genes most of which were not previously recognized as FVIIa regulated. All genes regulated by FVIIa were similarly regulated by a PAR2 agonist peptide confirming FVIIa signaling via PAR2. An appreciable fraction of the PAR2-regulated genes was also regulated by a PARI agonist peptide suggesting extensive redundancy between FVIIa/PAR2 signaling and thrombin/ PARI signaling. The FVIIa regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell signaling in MDA-MB-231 cells were regulated by thrombin and a PARI agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell line.