Co-expression of beta-adrenergic receptors and cyclooxygenase-2 in pulmonary adenocarcinoma

Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer and is hi ghly resistant to conventional cancer therapy. A better understanding, of t he regulatory mechanisms which control the growth of this deadly malignancy are urgently needed to develop more effective cancer intervention strategi es. Recent studies have shown that PAC frequently overexpresses cyclooxygen ase-2 (COX-2). This enzyme converts arachidonic acid (AA) into several meta bolites, some of which have been identified as modulators of mitogenesis an d apoptosis. Accordingly, the AA cascade and COX-2 are currently widely stu died as potential targets for lung cancer prevention. Recent studies by our research group have shown that cell lines derived from human PACs express beta (1)- and beta (2)-adrenergic receptors, which regulate the release of AA and DNA synthesis. Moreover, we have demonstrated that an antagonist for beta -adrenergic receptors or aspirin inhibited the development of experim entally induced PAC in a hamster model. These findings suggest that beta -a drenergic receptors may serve as upstream regulators of AA and COX-2-mediat ed PAC growth. However, no information is currently available on the expres sion of beta -adrenergic receptors and its possible correlation with the ex pression of COX-2 in tissue samples from human PAC, casting some doubt on t he significance of these findings in vitro and in an animal model. In the c urrent study, we have therefore analyzed tissue samples of human PACs for t he expression of beta (1)- and beta (2)-adrenergic receptors as well as COX -2 by reverse transcription polymerase chain reaction (RT-PCR) or immunohis tochemistry. Our data show that seven out of eight samples co-expressed COX -2 and one or both of these beta -adrenergic receptors, supporting the expe rimental evidence for a functional link between these neurotransmitter rece ptors and the AA cascade in the regulation of human PAC.