转录因子ERG可增加前列腺癌细胞上神经递质受体的表达。

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

作者信息

Kissick Haydn T, On Seung T, Dunn Laura K, Sanda Martin G, Asara John M, Pellegrini Kathryn L, Noel Jonathan K, Arredouani Mohamed S

机构信息

Department of Urology, Emory University School of Medicine, Atlanta, GA, USA.

Department of Surgery, Urology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 3 Blackfan Circle, E/CLS-446, Boston, MA, 02215, USA.

出版信息

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

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.

背景

TMPRSS2-ERG基因融合发生在大约一半的前列腺癌（PCa）病例中，并导致转录因子ERG的过表达。ERG的过表达对细胞功能有多种影响。然而，这些变化如何增强细胞生长并促进肿瘤发展尚不清楚。

方法

为了研究ERG的作用，用ERG转染LNCaP和PC3细胞，并分析基因表达和代谢谱。

结果

我们的数据表明，ERG的表达诱导许多烟碱型乙酰胆碱受体（nAChRs）的过表达。此外，通过LC-MS/MS进行的代谢谱分析显示，在表达ERG的细胞中几种神经递质的产生增加。一致地，用尼古丁处理表达ERG的细胞会诱导钙内流增加、GSK3β（Ser9）磷酸化和细胞增殖。最后，我们表明，如果前列腺癌患者的肿瘤是TMPRSS2-ERG基因融合阳性，那么吸烟者的肿瘤更大。