COX-2 gene polymorphisms and protein expression in renomedullary interstitial cell tumors.

Normal medullary interstitial cells regulate blood flow, water and salt absorption, and ultimately blood pressure through synthesis and secretion of prostanoids in which cycloxygenases play the rate-limiting steps. We found that most renomedullary interstitial cell tumors overexpressed cycloxygenase-2 (COX-2), with concomitant expression of microsomal prostaglandin E synthase-1 and the receptor for prostaglandin E2. Prostaglandin E2 is the major prostaglandin product of COX-2/microsomal prostaglandin E synthase-1 enzymatic pathway in medullary interstitial cells, and concomitant expression of COX-2, microsomal prostaglandin E synthase-1, and prostaglandin E2 receptor on interstitial cell tumors implies the presence of an autocrine growth loop important in pathogenesis of these tumors. Furthermore, overexpression of COX-2 protein was observed in association with homozygosity in several polymorphic sites within COX-2 gene (promoter region sites -1186 T/T and -765 G/G, intron 5 IVS5-275 T/T, and exon 10 Ex10+837 T>C), indicating their role in development of these tumors.