BMC Cancer 2005, 5:104 http://www.biomedcentral.com/1471-2407/5/104 IaFUngi5hog0inub4irst8eti8oiH9nsoopfrportoerliefenroaltiaonnditnhHe6G9IRcKellcshbaynntheel iβn-haibdirteonrergic Inhibition of proliferation in H69 cells by the β-adren- ergic agonist isoproterenol and the GIRK channel inhibitor U50488H. H69 cells were grown in the presence of isoproterenol or U50488H or a combination of Iso and U5 for 48 hours. Proliferation was determined by a BrdU assay. Both 10 µ M Iso (p < 0.001) and 2 µ M U5 (p < 0.001) inhibited proliferation with Iso having the greater effect. The effect of the GIRK inhibitor U5 on proliferation was potenti- ated by Iso (p < 0.001). N = 5. The tobacco carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK), a high affinity agonist for β- adrenergic receptors, stimulated DNA synthesis in two breast cancer cell lines, an effect inhibited by ICI [9]. In the present report the β-adrenergic agonist, Iso, inhibited proliferation in H69 SCLC cells, also indicating opposite effects between breast cancer and small cell lung cancer with β-adrenergic agonists. The GIRK channel inhibitor U5 [28] also inhibited proliferation. It is our contention that the same receptors and channels (β-adrenergic, GIRK) are in both breast cancer and lung cancer, and stim- ulation of these pathways can lead to different results. This could be important in devising therapies in women breast cancer patients that are also smokers. Another study has indicated down-regulation of protein synthesis and mRNA expression of voltage-dependent and calcium-acti- vated potassium channels bronchial and bronchiolar smooth muscle cells in rats by chronic smoking [35]. No differences were found in protein extracted from the lung, however. Further studies are needed with RNA interference (RNAi) or small interfering RNA (siRNA) and additional β-adren- ergic agonists and antagonists to further determine the effects of GIRK1 and GIRK2 on β-adrenergic signaling in human lung cancer, especially studies on differences in GIRK protein expression. However, it appears that β- adrenergic signaling and GIRK channels are important in both SCLC and breast cancer. These findings may be important in devising therapies based on β-adrenergic sig- naling and GIRK channel expression in lung cancers that express GIRK channels or β-adrenergic receptors. Conclusion We feel that this data may indicate that stimulation of GIRK1 or GIRK2 channels may be important in lung can- cer. Stimulation of GIRK channels and β-adrenergic sign- aling may activate similar signaling pathways in both SCLC and breast cancer, but lead to different results. Competing interests The author(s) declare that they have no competing interests. Authors' contributions HP carried out the majority of experiments, designed the study, and helped draft the manuscript. MD carried out the GIRK western blots. MD and MC were involved in pro- liferation studies. MC was also involved in RT-PCR. HS helped draft the manuscript. Acknowledgements Research described in this article was supported in part by Philip Morris USA Inc. and by Philip Morris International. This research was also sup- ported by a State of Tennessee Center of Excellence Fund grant to Dr. H.K. Plummer III. The WBA SCLC cell line was provided by Dr. G. Krystal, Med- ical College of Virginia, Richmond, VA. Expert editorial assistance was pro- vided by Dr. T. Masi. Cell culture support for BrdU assays was provided by Ms A. Gardner. References 1. 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