Abstract 5298: Regulation of urothelial bladder cancer by nicotine and stress neurotransmitters

Abstract

Abstract Urothelial bladder cancer (UBC) is the 7th most common cancer in men and the 17th most common cancer in women. Smoking is an established risk factor for UBC. However, the mechanisms how smoking induces bladder cancer are poorly understood. Using two established human urothelial bladder cancer cell lines, our data show that nicotine significantly increased the proliferation of both cell lines. Both cell lines produced the stress neurotransmitters norepinephrine and epinephrine and nicotine further enhanced this activity. The broad-spectrum beta-blocker propranolol strongly inhibited base level and nicotine-induced proliferation in both cell lines, identifying beta-adrenergic receptors as mediators. Proliferation in response to exogenous addition of epinephrine, norepinephrine or the selective β-adrenergic agonist isoproterenol and complete blockage of these responses by propranolol support this interpretation. Treatment with the inhibitory neurotransmitter γ-aminobutyric acid (GABA), that inhibits beta-adrenergic receptor-mediated proliferation of other cancer types via inhibition of cAMP formation, was less effective. These findings suggest that urothelial bladder cancer cells are stimulated in their growth via beta-adrenergic receptor signaling independent of cAMP by nicotine or psychological stress. Additional investigations are underway to further dissect the signal transduction pathways involved. Supported by the State of Tennessee Center of Excellence in Livestock Diseases and Human Health. Citation Format: Arokya M. Papu John, Jheelam Banerjee, Hildegard M. Schuller. Regulation of urothelial bladder cancer by nicotine and stress neurotransmitters. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5298. doi:10.1158/1538-7445.AM2014-5298