title: Overexpression of arginine transporter CAT-1 is associated with accumulation of L-arginine and cell growth in human colorectal cancer tissue.
abstract: 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.
authors.affiliation: Clinical Translational Medical Research Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Weimin
authors.initials: W
authors.lastname: Wang
authors.forename: Junchen
authors.initials: J
authors.lastname: Wang
authors.forename: Chunzhang
authors.initials: C
authors.lastname: Yang
authors.forename: Huiming
authors.initials: H
authors.lastname: Mao
authors.forename: Xuelian
authors.initials: X
authors.lastname: Fu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wu
authors.forename: Jingping
authors.initials: J
authors.lastname: Cai
authors.forename: Junyi
authors.initials: J
authors.lastname: Han
authors.forename: Zengguang
authors.initials: Z
authors.lastname: Xu
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.forename: Bingguan
authors.initials: B
authors.lastname: Chen
mesh_terms: D000368:Aged; D001120:Arginine / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002956:Citrulline / Q000097:blood / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034622:RNA Interference
chemical_list: D027201:Cationic Amino Acid Transporter 1; D002956:Citrulline; D001120:Arginine
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