The expression of prostaglandin H synthases can be induced by many stimuli and is likely to be important in control of the cell cycle. The analysis of prostaglandin H synthase-1 and -2 expression in colon adenocarcinoma cell lines is a useful model system for studying the function of the prostaglandin H synthases, especially with regard to proliferation and adhesion. Prostaglandin H synthase-1 protein is not found in any of eight human colon adenocarcinoma cell lines. Expression of prostaglandin H synthase-2 is variable for the eight cell lines: three constitutively 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 prostaglandin H synthase-2 produce PGE2. Prostaglandin E2 production could be inhibited by aspirin and NS398 without inhibiting proliferation, while direct addition of prostaglandin E2 inhibits proliferation. Adhesion to collagen IV and fibronectin was stronger in those cell lines that expressed prostaglandin H synthase-2. The constitutive expression of prostaglandin H synthase-2 is associated with increased adhesion to extracellular matrix components and a potential inhibition of proliferation through the production of prostaglandin E2. The absence of PGH synthase-2 expression in some cell lines may result from the original tumor's need to inactivate these associated functions. Our evidence suggests that PGH synthase-2 is a possible candidate for a tumor suppressor gene at 1q23-qter.