Inducible prostaglandin E synthase is overexpressed in non-small cell lungcancer

An inducible microsomal form of human prostaglandin E synthase (mPGES) was recently identified. This enzyme converts the cyclooxygenase (COX) product, prostaglandin (PG) H-2 to PGE(2), a prostanoid that has been implicated in carcinogenesis. Increased amounts of PGE2 are detected in many types of ca ncer, but the underlying mechanism is not fully understood. Hence, we compa red amounts of mPGES in 19 paired samples (tumor and adjacent normal tissue ) of non-small cell lung cancer (NSCLC). By immunoblot analysis, mPGES was overexpressed in about 80% of NSCLCs. Immunohistochemistry localized the ex pression of mPGES to neoplastic epithelial cells. COX-2 was also commonly u p-regulated in these tumors; marked differences in the extent of up-regulat ion of mPGES and COX-2 were observed in individual tumors. Cell culture was used to define the underlying mechanism(s) that accounts for up-regulation of mPGES in NSCLC. As reported previously for COX-2, levels of mPGES mRNA and protein were increased in NSCLC cell lines containing mutant Ras as com pared with a nontumorigenic bronchial epithelial cell line. Nuclear run-off s revealed increased rates of mPGES transcription in the transformed cell l ines. Overexpression of Ras caused a severalfold increase in mPGES promoter activity in nontransformed cells. Tumor necrosis factor-alpha induced mPGE S and COX-2 in NSCLC cell lines but had no effect on the expression of eith er enzyme in a nontumorigenic bronchial epithelial cell line. Consistent wi th prior observations for COX-2, these data suggest that both cellular tran sformation and cytokines contribute to the up-regulation of mPGES in NSCLC.