The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells

• Type of Material: Article
• Authors: Haydn Kissick, Emory University; Seung T. On, Emory University; Laura K. Dunn, Emory University; Martin G. Sanda, Emory University; John M. Asara, Emory University; Kathryn L. Pellegrini, Emory University; Jonathan K. Noel, Emory University; Mohamed S. Arredouani, Emory University
• Language: English
• Date: 2015-08-27
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © Kissick et al. 2015
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12885-015-1612-3
• Title of Journal or Parent Work: BMC Cancer
• ISSN: 1471-2407
• Volume: 15
• Issue: 604
• Grant/Funding Information: The work was partially supported by NIH grants 5P01CA120964 (J.M. Asara), 5P30CA006516 (J.M. Asara), the NIH-National Cancer Institute Early Detection Research Network grant UO1-CA113913 (M.G. Sanda), the National Cancer Institute Prostate Specialized Program of Research Excellence Career Development Award 2P50CA90381-06 (M.S. Arredouani), the Prostate Cancer Foundation Young Investigator Award (M.S. Arredouani), the Prostate Cancer Foundation A. Mazzone Challenge Award (M.G. Sanda and M.S. Arredouani), the Department of Defense Prostate Cancer Research Program New Investigator Award W81XWH-09-1-0448 (M.S. Arredouani), Department of Defense Prostate Cancer Research Program Laboratory-Clinical Transition Award W81XWH-09-1-0156 (M.S. Arredouani & M.G. Sanda, Co-PI), US Department of Defense Prostate Cancer Research Program Laboratory-Postdoctoral Training Award W81XWH-13-1-0246 (H.T. Kissick).
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

Background The TMPRSS2-ERG gene fusion occurs in about half of prostate cancer (PCa) cases and results in overexpression of the transcription factor ERG. Overexpression of ERG has many effects on cellular function. However, how these changes enhance cell growth and promote tumor development is unclear. Methods To investigate the role of ERG, LNCaP and PC3 cells were transfected with ERG and gene expression and metabolic profile were analyzed. Results Our data show that expression of ERG induces overexpression of many nicotinicacetylcholine receptors (nAChRs). In addition, metabolic profiling by LC-MS/MS revealed elevated production of several neurotransmitters in cells expressing ERG. Consistently, treatment of ERG-expressing cells with nicotine induced elevated calcium influx, GSK3β (Ser9) phosphorylation and cell proliferation. Finally, we show that PCa patientswho are smokers have larger tumors if their tumors are TMPRSS2-ERG gene fusion positive. Conclusion Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1612-3) contains supplementary material, which is available to authorized users.