COX-2 expression and cell cycle progression in human fibroblasts

Cyclooxygenase-2 (COX-2) is continuously expressed in most cancerous cells where it appears to modulate cellular proliferation and apoptosis. However, little is known about the contribution of transient COX-2 induction to cell cycle progression or programmed cell death in primary cells. In this study we determined whether COX-2 regulates proliferation or apoptosis in human fibroblasts. COX-2 mRNA, protein, and prostaglandin E-2 (PGE(2)) were not detected in quiescent cells but were expressed during the G(0)/G(1) phase of the cell cycle induced by serum. Inhibition of COX-2 did not alter G(0)/G(1) to S phase transition or induce apoptosis at concentrations that diminished PGE(2). Addition of interleukin-1 beta to serum enhanced COX-2 expression and PGE(2) synthesis over that by serum alone but had no effect on the progression of these cells into S phase. Furthermore, platelet-derived growth factor drove the G(0) fibroblasts into the cell cycle without inducing detectable levels of COX-2 or PGE(2). Collectively, these data show that transient COX-2 expression in primary human fibroblasts does not influence cell cycle progression.