The Study On Cyclooxygenase-2 (COX-2) In FBJ Cells

Cyclooxygenease-2 (COX-2) a key enzyme regulating the production of prostaglandins, is known to be closely associated with tumor growth and metastasis in several kinds of human tumors. I have shown that the expression of COX-2 in highly metastasis FBJ-LL cells was 59 times as much as that in poorly metastasis FBJ-S1. FBJ-LL cells are highly metastatic and poor in ganglioside GD1a and caveolin-1 (Cav-1), whereas FBJ-S1 cells are poorly metastatic and rich in GD1a and Cav-1. Positively regulation of Cav-1 by ganglioside GD1a has been alreadyelucidated in the laboratory in 2006. I have under taken to illustrate how COX-2 is regulated in FBJ cells. In this paper, I have describled that GD1a regulates COX-2 expression possibly through Cav-1, but the involvement of Wnt signal has been doubtful, since GSK-3βinhibitor failed to block COX-2 stimulation. The expression was also known mediated by NFκB, which was not involved in COX-2 expression on stimulation by TNFasignal. cyclic AMP (cAMP) was found to stimulate COX-2 through EPAC pathway; involvement of PKA has been rule out. This is the first report on the involvement of EPAC on COX-2 stimulation in science. ERK1/2 inhibitor impaired COX-2 expression and ERK1/2-silienced transfectants decreased COX-2 as well as ERK1/2 expression, suggesting positive involvement of ERK1/2 in COX-2 regulation. Cyclosporine A (inhibitor of calcinurin), two antagonists of calmodulin (W-7, TFP) and inctracellular Ca2+ antagonist (HA-1077), all have stimulated COX-2 expression in FBJ cells, suggesting that calcium is used as an inhibitory signal in FBJ cells, contrary to all the reports in the past. Thus FBJ cells have an unique machinery for COX-2 regulation. Which awaits further analyses.