title: Co-expression of beta-adrenergic receptors and cyclooxygenase-2 in pulmonary adenocarcinoma.
abstract: Pulmonary adenocarcinoma (PAC) is the leading type of lung cancer and is highly resistant to conventional cancer therapy. A better understanding of the regulatory mechanisms which control the growth of this deadly malignancy are urgently needed to develop more effective cancer intervention strategies. Recent studies have shown that PAC frequently overexpresses cyclooxygenase-2 (COX-2). This enzyme converts arachidonic acid (AA) into several metabolites, some of which have been identified as modulators of mitogenesis and apoptosis. Accordingly, the AA cascade and COX-2 are currently widely studied as potential targets for lung cancer prevention. Recent studies by our research group have shown that cell lines derived from human PACs express beta1- and beta2-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 experimentally induced PAC in a hamster model. These findings suggest that beta-adrenergic receptors may serve as upstream regulators of AA and COX-2-mediated PAC growth. However, no information is currently available on the expression of beta-adrenergic receptors and its possible correlation with the expression of COX-2 in tissue samples from human PAC, casting some doubt on the significance of these findings in vitro and in an animal model. In the current study, we have therefore analyzed tissue samples of human PACs for the expression of beta1-and beta2-adrenergic receptors as well as COX-2 by reverse transcription polymerase chain reaction (RT-PCR) or immunohistochemistry. Our data show that seven out of eight samples co-expressed COX-2 and one or both of these beta-adrenergic receptors, supporting the experimental evidence for a functional link between these neurotransmitter receptors and the AA cascade in the regulation of human PAC.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996, USA. hmsch@utk.edu
authors.forename: H M
authors.initials: HM
authors.lastname: Schuller
authors.forename: H K
authors.initials: HK
authors.lastname: Plummer
authors.forename: P N
authors.initials: PN
authors.lastname: Bochsler
authors.forename: P
authors.initials: P
authors.lastname: Dudric
authors.forename: J L
authors.initials: JL
authors.lastname: Bell
authors.forename: R E
authors.initials: RE
authors.lastname: Harris
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D051546:Cyclooxygenase 2; D017931:DNA Primers / Q000737:chemistry; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism*; D008565:Membrane Proteins; D016612:Paraffin Embedding; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases