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BMC Cancer. 2015 Aug 27;15:604. doi: 10.1186/s12885-015-1612-3.

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

Author information

1
Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. haydn.kissick@emory.edu.
2
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.
3
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.
4
Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. martin.sanda@emory.edu.
5
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. jasara@bidmc.harvard.edu.
6
Department of Urology, Emory University School of Medicine, Atlanta, GA, USA. Kathryn.pellegrini@emory.edu.
7
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.
8
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.

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.

PMID:
26310325
PMCID:
PMC4549934
DOI:
10.1186/s12885-015-1612-3
[Indexed for MEDLINE]
Free PMC Article

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