Differential expression of cyclooxygenase-2 and its regulation by tumor necrosis factor-alpha in normal and malignant prostate cells

Cyclooxygenase (COX)-2 expression is elevated in some malignancies; however , information is scarce regarding COX-2 contributions to the development of prostate cancer and its regulation by inflammatory cytokines. The present study compared and contrasted the expression levels and subcellular distrib ution patterns of COX-1 and COX-2 in normal prostate [prostate epithelial c ell (PrEC), prostate smooth muscle (PrSM), and prostate stromal (PrSt)] pri mary cell cultures and prostatic carcinoma cell lines (PC-3, LNCaP, and DU1 45), The basal COX-2 mRNA and protein levels were high in normal PrEC and l ow in tumor cells, unlike many other normal cells and tumor cells. Because COX 2 levels were low in prostate smooth muscle cells, prostate stromal cel ls, and tumor cells, we also examined whether COX-1 and COX-2 gene expressi on was elevated in response to tumor necrosis factor-alpha (TNF-alpha), a s trong inducer of COX-2 expression. Northern blot analysis and reverse trans cription-PCR demonstrated different patterns and kinetics of expression for COX-1 and COX-2 among normal cells and tumor cells in response to TNF-alph a. In particular, COX-2 protein levels increased, and the subcellular distr ibution formed a distinct perinuclear ring in the normal cells at 3 h after TNF-alpha exposure. The COX-2 protein levels also increased in cancer cell s, but the subcellular distribution was less organized; COX-2 protein appea red diffuse in some cells and accumulated as focal deposits in the cytoplas m of other cells, TNF-alpha induction of COX-2 and prostaglandin E-2 correl ated inversely with induction of apoptosis. We conclude that COX-2 expressi on may be important to PrEC cell function. Although it is low in stromal an d tumor cells, COX-2 expression is induced by TNF-alpha in these cells, and this responsiveness may play an important role in prostate cancer progress ion.