Reciprocal regulation of cyclooxygenase-2 and 15-hydroxyprostaglandin dehydrogenase expression in A549 human lung adenocarcinoma cells

Carcinogenesis
Min TongHsin-Hsiung Tai

Abstract

Human lung adenocarcinoma cells, A549, possess the capacity of expressing both cyclooxygenase-2 (COX-2) and NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Resting cells express little COX-2 but significant levels of 15-PGDH. Interleukin (IL) 1beta, tumor necrosis factor-alpha (TNF-alpha) or phorbol ester [phorbol 12-myristate 13-acetate (PMA)] induced the expression of COX-2, as revealed by western blot analysis. Combination of PMA and IL-1beta or TNF-alpha induced synergistically the expression of COX-2. Interestingly, cytokines and cytokine plus PMA-induced expression of COX-2 were accompanied by a downregulation of 15-PGDH. This was evident from both the western blot analysis and activity assay of 15-PGDH. It appears that the higher the expression of COX-2 was induced, the lower the expression of 15-PGDH was found. This was further supported by the observation that overexpression of COX-2 but not COX-1 by adenovirus-mediated approach led to a decrease in 15-PGDH expression, indicating the specificity of COX-2. Furthermore, downregulation of the IL-1beta-induced expression of COX-2 by silencing RNA (siRNA) approach resulted in an increase in the expression of 15-PGDH by COX-2-siRNA but not by COX-1-siRNA, indica...Continue Reading

Citations

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