Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells.
Sarcosine induces increase in HER2/neu expression in androgen-dependent prostate cancer cells.
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DOI：
10.1007/s11033-010-0442-2
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发表时间：
2011-10
影响因子：
2.8
通讯作者：
Bouchelouche K
中科院分区：
文献类型：
--
作者：
Dahl M;Bouchelouche P;Kramer-Marek G;Capala J;Nordling J;Bouchelouche K
越来越多的证据表明，人表皮生长因子受体2 （HER2/neu）参与前列腺癌的进展。最近，据报道，在前列腺癌的进展过程中，肌氨酸水平高度增加，外源性肌氨酸在良性前列腺上皮细胞中诱导侵袭性表型。本研究的目的是研究肌氨酸对前列腺癌细胞LNCaP（雄激素依赖性）、PC-3和DU145（雄激素非依赖性）中HER2/neu表达的影响。使用RT-qPCR测定HER2/neu和雄激素受体（AR）转录本的相对量。Western blot （WB）检测HER2/neu的总表达量。使用HER2/neu特异性荧光探针，共聚焦显微镜观察LNCaP细胞表面的HER2/neu蛋白。LNCaP细胞暴露于50 μM肌肉氨酸24 h后，HER2/neu mRNA水平升高58% (p<0.001)，表明肌肉氨酸对HER2/neu表达的转录水平有影响。对照实验显示，肌氨酸的异构体丙氨酸对HER2/neu转录没有显著影响。WB和共聚焦显微镜显示，在肌氨酸暴露48小时后，HER2/neu mRNA的上调先于蛋白质水平的相应增加。有趣的是，肌氨酸对活化（磷酸化）的HER2/neu没有影响。肌氨酸暴露后AR表达未见明显变化。这是第一个表明肌氨酸参与肿瘤蛋白HER2/neu调控的报道。因此，肌氨酸可能通过增加HER2/neu表达来诱导前列腺癌的进展。然而，关于细胞机制的详细信息仍有待阐明。
Increasing evidence suggests that Human epidermal growth factor receptor 2 (HER2/neu) is involved in progression of prostate cancer. Recently, sarcosine was reported to be highly increased during prostate cancer progression, and exogenous sarcosine induces an invasive phenotype in benign prostate epithelial cells. The aim of this work was to investigate the effect of sarcosine on HER2/neu expression in prostate cancer cell lines LNCaP (androgen dependent), PC-3 and DU145(both androgen independent). Relative amounts of HER2/neu and androgen receptor (AR) transcripts were determined using RT-qPCR. Total expression of HER2/neu was confirmed by Western blot (WB). HER2/neu protein on the surface of living LNCaP cells was visualized by confocal microscopy using a HER2/neu-specific fluorescent probe. Exposure of LNCaP cells to 50 μM sarcosine for 24 h resulted in a 58% increase of the HER2/neu mRNA level (p<0.001) indicating that sarcosine effects HER2/neu expression on the level of transcription. Control experiments with alanine, an isomer of sarcosine, showed no significant effect on HER2/neu transcription. The upregulation of HER2/neu mRNA preceded the corresponding increment of the protein level after the 48-h exposure to sarcosine as shown by WB and confocal microscopy. Interestingly, sarcosine had no effect on the activated (phosphorylated) form of HER2/neu. No significant change in AR expression was observed after exposure to sarcosine. This is the first report indicating that sarcosine is involved in the regulation of the oncoprotein HER2/neu. Thus, sarcosine may induce prostate cancer progression by increased HER2/neu expression. However, detailed information on cellular mechanisms remains to be elucidated.
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影响因子：
64.8
作者：
Sreekumar, Arun;Poisson, Laila M.;Rajendiran, Thekkelnaycke M.;Khan, Amjad P.;Cao, Qi;Yu, Jindan;Laxman, Bharathi;Mehra, Rohit;Lonigro, Robert J.;Li, Yong;Nyati, Mukesh K.;Ahsan, Aarif;Kalyana-Sundaram, Shanker;Han, Bo;Cao, Xuhong;Byun, Jaeman;Omenn, Gilbert S.;Ghosh, Debashis;Pennathur, Subramaniam;Alexander, Danny C.;Berger, Alvin;Shuster, Jeffrey R.;Wei, John T.;Varambally, Sooryanarayana;Beecher, Christopher;Chinnaiyan, Arul M.
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Chinnaiyan, Arul M.
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8
作者：
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通讯作者：
Baldwin, A. S.
影响因子：
11.2
作者：
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通讯作者：
Loda, Massimo
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
50.5
作者：
Rubin, I;Yarden, Y
通讯作者：
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