PROSTAGLANDIN-H SYNTHASE EXPRESSION IS VARIABLE IN HUMAN COLORECTAL ADENOCARCINOMA CELL-LINES

The expression of prostaglandin H synthases can be induced by many sti muli and is likely to be important in control of the cell cycle, The a nalysis of prostaglandin H synthase-1 and -2 expression in colon adeno carcinoma cell lines is a useful model system for studying the functio n of the prostaglandin H synthases, especially with regard to prolifer ation and adhesion, Prostaglandin H synthase-1 protein is not found in any of eight human colon adenocarcinoma cell lines. Expression of pro staglandin H synthase-2 is variable for the eight cell lines: three co nstitutively expressed active protein, four did not express this gene at all, and one had mRNA but no active protein. Thus, five colorectal adenocarcinoma cell lines exhibit ''null'' expression of prostaglandin synthase-2. The three cell lines with constitutive expression of pros taglandin H synthase-2 produce PGE(2). Prostaglandin E-2 production co uld be inhibited by aspirin and NS398 without inhibiting proliferation , while direct addition of prostaglandin E-2 inhibits proliferation. A dhesion to collagen IV and fibronectin was stronger in those cell line s that expressed prostaglandin H synthase-2. The constitutive expressi on of prostaglandin H synthase-2 is associated with increased adhesion to extracellular matrix components and a potential inhibition of prol iferation through the production of prostaglandin E-2. The absence of PGH synthase-2 expression in some cell lines may result from the origi nal tumor's need to inactivate these associated functions. Our evidenc e suggests that PGH synthase-2 is a possible candidate for a tumor sup pressor gene at 1q23-qter. (C) 1997 Academic Press.