title: The transcription factor ERG increases expression of neurotransmitter receptors on prostate cancer cells.
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.
  
  
  CONCLUSIONS
  Collectively, our data suggest that ERG sensitizes prostate tumor cells to neurotransmitter receptor agonists like nicotine.
authors: Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. haydn.kissick@emory.edu.
authors: Haydn T
authors: HT
authors: Kissick
authors: Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, E/CLS-446, Boston, MA, 02215, USA. seungtae.on@my.mcphs.edu.
authors: Seung T
authors: ST
authors: On
authors: Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, E/CLS-446, Boston, MA, 02215, USA. laurdunn@gmail.com.
authors: Laura K
authors: LK
authors: Dunn
authors: Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. martin.sanda@emory.edu.
authors: Martin G
authors: MG
authors: Sanda
authors: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. jasara@bidmc.harvard.edu.
authors: John M
authors: JM
authors: Asara
authors: Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. Kathryn.pellegrini@emory.edu.
authors: Kathryn L
authors: KL
authors: Pellegrini
authors: Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, E/CLS-446, Boston, MA, 02215, USA. jknoel@hotmail.com.
authors: Jonathan K
authors: JK
authors: Noel
authors: Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, E/CLS-446, Boston, MA, 02215, USA. simo.arredouani@agenusbio.com.
authors: Mohamed S
authors: MS
authors: Arredouani
mesh_terms: D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008297:Male; D055442:Metabolome; D009538:Nicotine / Q000494:pharmacology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D015854:Up-Regulation
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; D011978:Receptors, Nicotinic; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D009538:Nicotine; D002118:Calcium