Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue.
Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue.
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DOI：
10.1371/journal.pone.0073866
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen B
中科院分区：
文献类型：
--
作者：
Lu Y;Wang W;Wang J;Yang C;Mao H;Fu X;Wu Y;Cai J;Han J;Xu Z;Zhuang Z;Liu Z;Hu H;Chen B
我们之前发现l -精氨酸（Arg）在结直肠癌组织中积累。本研究的目的是探讨精氨酸积累的机制，并确定其生物学意义。采用高效液相色谱法（HPLC）对结直肠癌（CRC）患者血清和肿瘤组织中精氨酸（Arg）和瓜氨酸（Cit）的含量进行了分析。采用定量逆转录聚合酶链反应（qRT-PCR）和组织芯片免疫组化分析Arg转运体的表达。我们还用Arg转运体CAT-1特异性siRNA转染结肠癌细胞系HCT-116，并通过流式细胞术和MTT法检测其诱导凋亡和细胞增殖情况。与我们之前的结果一致，结直肠癌患者血清Arg和Cit浓度明显低于正常志愿者，而结直肠癌组织中Arg和Cit浓度明显高于匹配的邻近正常结肠组织。定量RT-PCR结果显示，在122例结直肠癌患者中，70.5%的结直肠癌组织样本中CAT-1基因相对于邻近正常结肠组织高度过表达。组织芯片免疫组化分析证实，CAT-1在25个结直肠癌组织中的表达均较高。CAT-1 siRNA显著诱导HCT-116细胞凋亡，随后抑制细胞生长20-50%。我们的研究结果表明，结直肠癌组织中L-Arg和Cit的积累和细胞生长与Arg转运体基因CAT-1的过度表达有关。我们的结果可能对开发结直肠癌的分子诊断工具和靶向治疗有帮助。
We previously showed that L-arginine (Arg) accumulates in colorectal cancer tissues. The aim of this study was to investigate the mechanism by which Arg accumulates and determine its biological significance. The concentration of Arg and Citrulline (Cit) in sera and tumor tissues from colorectal cancer (CRC) patients was analyzed by high-performance liquid chromatography (HPLC). The expression of Arg transporters was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis of tissue microarray. We also transfected the colon cancer cell line HCT-116 with siRNA specific for the Arg transporter CAT-1 and measured the induction of apoptosis by flow cytometry and cell proliferation by MTT assay. Consistent with our previous results, serum Arg and Cit concentrations in colorectal cancer patients were significantly lower than those in normal volunteers, while Arg and Cit concentrations in colorectal cancer tissues were significantly higher than in matched adjacent normal colon tissues. Quantitative RT-PCR showed that the CAT-1 gene was highly overexpressed in 70.5% of colorectal cancer tissue samples relative to adjacent normal colon tissues in all 122 patients with colorectal cancer. Immunohistochemical analysis of tissue microarray confirmed that the expression of CAT-1 was higher in all 25 colorectal cancer tissues tested. CAT-1 siRNA significantly induced apoptosis of HCT-116 cells and subsequently inhibited cell growth by 20–50%. Our findings indicate that accumulation of L-Arg and Cit and cell growth in colorectal cancer tissues is associated with over-expression of the Arg transporter gene CAT-1. Our results may be useful for the development of molecular diagnostic tools and targeted therapy for colorectal cancer.
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影响因子：
11.2
作者：
Kim, Randie H.;Coates, Jodi M.;Bowles, Tawnya L.;McNerney, Gregory P.;Sutcliffe, Julie;Jung, Jae U.;Gandour-Edwards, Regina;Chuang, Frank Y. S.;Bold, Richard J.;Kung, Hsing Jien
通讯作者：
Kung, Hsing Jien
影响因子：
6.2
作者：
Dillon, BJ;Prieto, VG;Clark, MA
通讯作者：
Clark, MA
影响因子：
4.2
作者：
Closs, EI;Simon, A;Rotmann, A
通讯作者：
Rotmann, A
DOI：
10.1186/1878-5085-4-3
发表时间：
2013-01-28
期刊：
The EPMA journal
影响因子：
--
作者：
Hagan S;Orr MC;Doyle B
通讯作者：
Doyle B
影响因子：
11.2
作者：
Lahdenranta J;Hagendoorn J;Padera TP;Hoshida T;Nelson G;Kashiwagi S;Jain RK;Fukumura D
通讯作者：
Fukumura D