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SLC38A1基因在胃癌发生发展中的作用研究
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摘要
胃癌是我国常见肿瘤之一,寻找有效的分子标志物成为了当前亟待解决的热点和难点。我们前期建立了胃癌及癌旁正常胃黏膜组织的基因表达谱,利用基因芯片技术得到一组差异表达基因,其中SLC38A1在胃癌组织中呈显著高表达。本研究应用Real-time PCR、WB技术检测SLC38A1在人胃癌细胞系、新鲜胃癌组织样本中的表达水平,初步验证表达谱的结果;采用组织芯片技术进一步检测1072例中国胃癌患者中该基因的表达情况,并分析该基因与胃癌患者临床病理参数之间的关系;利用细胞功能学实验观察SLC38A1基因RNA干扰后对细胞增殖、凋亡、迁移、侵袭等的影响,探讨其在胃癌发生发展中的可能作用机制。
Gastric cancer is the most common malignant tumor in China. So it will be crucial not only for understanding the molecular mechanisms underlying development and progression, but also for finding a putative biomarker of tumor prognosis and for formulating more effective therapeutic targets. We used DNA microarray to analysize gene expression differences between gastric cancer and normal tissues, and after the confirmation of PCR&WB, we selected SLC38A1 as the interested gene. And we used tissue microarray blocks containing gastric cancer tissue and matched noncancer gastric tissue specimens and in vitro studies to detect the expression of SLC38A1 in Chinese patients with gastric cancer and its clinical effects; We also performed some experiments to explore the underlying mechanisms.
引文
1. Christensen H N. Role of amino acid transport and counter-transport in nutrition and metabolism [J]. Physiol Rev 1990; 70:43-77.
    2. McGivan JD, Pastor-Anglada M. Regulatory and molecular aspects of mammalian amino acid transport[J]. Biochem J 1994; 299 (Pt 2):321-334.
    3. Lin J, Raoof DA, Thomas DG et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma[J]. Neoplasia 2004; 6:74-84.
    4. Kim DK, Ahn SG, Park JC et al. Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in oral squamous cell carcinoma and its precusor lesions[J]. Anticancer Res 2004; 24:1671-1675.
    5. Haase C, Bergmann R, Fuechtner F et al. L-type amino acid transporters LAT1 and LAT4 in cancer: uptake of 3-O-methyl-6-18F-fluoro-L-dopa in human adenocarcinoma and squamous cell carcinoma in vitro and in vivo[J]. J Nucl Med 2007; 48:2063-2071.
    6. Campbell WA, Thompson NL. Overexpression of LAT1/CD98 light chain is sufficient to increase system L-amino acid transport activity in mouse hepatocytes but not fibroblasts[J]. J Biol Chem 2001; 276:16877-16884.
    7. Kondoh N, Imazeki N, Arai M, et al. Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues[J]. Int J Oncol 2007; 31:81-87.
    8. Bhat HK, Vadgama JV. Role of estrogen receptor in the regulation of estrogen induced amino acid transport of System A in breast cancer and other receptor positive tumor cells[J]. Int J Mol Med 2002; 9: 271-279.
    9. Novak D, Quiggle F, Haafiz A. Impact of forskolin and amino acid depletion upon System A activity and SNAT expression in BeWo cells[J]. Biochimie 2006; 88:39-44.
    10. Seow H F, Brller S, Brtier A, et al. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19[J]. Nat Genet 2004;36:1003-1007.
    11. Kanai Y, Endou H. Functional properties of multispecific amino acid transpo rters and their implications to transporter-mediated toxicity[J]. J Toxicol Sci 2003;28:1-17.
    12. Moffett J, Englesberg E. Regulation of the A system of amino acid transport in Chinese hamster ovary cells, CHO-K1:the difference in specificity between the apo-repressor inactivator (apo-ri) and the transporter and the characterization of the proposed apo-ri[J]. J Cell Physiol 1986; 126:421-429.
    13. McCormick JI, Johnstone RM. Identification of the integrin alpha 3 beta 1 as a component of a partially purified A-system amino acid transporter from Ehrlich cell plasma membranes[J]. Biochem J 1995;311 (Pt 3):743-751.
    14. Utsunomiya-Tate N, Endou H, Kanai Y. Cloning and functional characterization of a system ASC-like Na+ -dependent neutral amino acid transporter[J]. J Biol Chem 1996; 271:14883-14890.
    15. Kanai Y, Fukasawa Y, Cha SH, et al. Transport properties of a system y+L neutral and basic amino acid transporter. Insights into the mechanisms of substrate recognition[J]. J Biol Chem 2000; 275: 20787-20793.
    16. Matsuo H, Tsukada S, Nakata T, et al. Expression of a system L neutral amino acid transporter at the blood-brain barrier[J]. Neuroreport 2000; 11:3507-3511.
    17.何庆华,孔祥峰,吴永宁,等.氨基酸转运载体研究进展[J].氨基酸和生物资源,2007;29(2):42-45.
    18. Varoqui H, Zhu H, Yao D, et al. Cloning and functional identification of a neuronal glutamine transporter[J]. J Biol Chem 2000; 275:4049-4054.
    19. Sugawara M, Nakanishi T, Fei YJ, et al. Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A[J]. J Biol Chem 2000; 275: 6473-16477.
    20. Hatanaka T, Huang W, Ling R, et al. Evidence for the transport of neutral as well as cationic amino acids by ATA3, a novel and liver-specific subtype of amino acid transport system A[J]. Biochim Biophys Acta 2001; 1510:10-17.
    21. Yoon JH, Kim IJ, Kim H, et al. Amino acid transport system L is differently expressed in human normal oral keratinocytes and human oral cancer cells[J]. Cancer Lett 2005; 222:237-245.
    22. Bhat HK and Vadgama JV:Role of estrogen receptor in the regulation of estrogen induced amino acid transport of System A in breast cancer and other receptor positive tumor cells[J]. Int J Mol Med 2002; 9:271-279.
    23. Dudeck KL, Dudenhausen EE, Chiles TC, et al. Evidence for inherent differences in the system A carrier from normal and transformed liver tissue. Differential inactivation and substrate protection in membrane vesicles and reconstituted proteoliposomes[J]. J Biol Chem 1987; 262:12565-12569.
    24. Nii T, Segawa H, Taketani Y, et al. Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation[J]. Biochem J 2001; 358(Pt 3):693-704.
    25. Easson AM, Bode BP, Fischer CP, Souba WW. Effects of endotoxin challenge on hepatic amino acid transport during cancer[J]. J Surg Res 1998; 77:29-34.
    26. NakanishiK, MatsuoH, KanaiY, et al. LAT1 expressionin normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung[J]. Virchows Arch 2006; 448(2):142-50.
    27. Rajan DP, KekudaR, HuangW, et al. Cloning and functional characterization of a Na+ -independent, broad-specific neutral amino acid transporter from mammalian intestine[J]. Biochim Biophys Acta 2000; 1463(1):6-14.
    28. Kim SG, Kim HH, Kim HK, et al. Diferential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells[J]. Anticancer Res 2006; 26(3A):1989-96.
    29. Simmons, Willis TA, Koh AS, Clarkson TW, et al. Transport of a neurotoxicant by molecular mimicry:the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter(LAT)1 and LAT2[J]. Biochem J 2002; 367(Pt 1):239-46.
    30. Lin J, Raoof DA, Thomas DG, et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma[J]. Neoplasia 2004; 6(1):74-84.
    31. Yoon JH, Kim IJ, Kiln H, et al. Amino acidt ransport system L is differently expressed in human norma oral keratinocytes And human oral cancer cells[J]. Cacer Lett 2005; 222(2):237-45.
    32. Yoon JH, Kim YB, Kim MS, et al. Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells[J]. Cancer Lett 2004; 205(2): 215-26.
    33. Baniasadi S, Chairoungdua A, Iribe Y, et al. Gene expression profiles in T24 human bladder carcinoma cells by inhibiting an L-type amino acid transporter, LAT1[J]. Arch Pharm Res 2007; 30(4):444-52.
    34. Nawashiro H, Otani N, Shinomiya N, et al. L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors[J]. Int J Cancer 2006; 119(3):484-92.
    35.. Wu Y, Shen D, Chen Z, et al. Taxol induced apoptosis regulates amino acid transport in breast cancer cells[J]. Apoptosis 2007; 12:593-612.
    36. ChristieGR, HajduchE, HundalHS, et al. Intracelular sensing of amino acids in Xenopuslaevis oocytes stimulates p70 S6 kinase in a target of rapamycin-depc ndent manner[J]. J Biol Chem 2002; 277(12):9952-7.
    37.邓敦.低蛋白日粮补充合成氨基酸对猪体营养代谢及其机理研究[Z].中国科学院亚热带农业生态研究所.2006.
    1. Dixit VM, Green S, Sarma V et al. Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J Biol Chem 1990; 265: 2973-2978.
    2. Beyaert R, Heyninck K, Van Huffel S. A20 and A20-binding proteins as cellular inhibitors of nuclear factor-kappa B-dependent gene expression and apoptosis. Biochem Pharmacol 2000; 60: 1143-1151.
    3. Onose A, Hashimoto S, Hayashi S et al. An inhibitory effect of A20 on NF-kappaB activation in airway epithelium upon influenza virus infection. Eur J Pharmacol 2006; 541:198-204.
    4. Lee EG, Boone DL, Chai S et al. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 2000; 289:2350-2354.
    5. Klinkenberg M, Van Huffel S, Heyninck K, Beyaert R. Functional redundancy of the zinc fingers of A20 for inhibition of NF-kB activation and protein-protein interactions. FEBS Lett 2001; 498:93-97.
    6. Heyninck K, Kreike MM, Beyaert R. Structure-function analysis of the A20-binding inhibitor of NF-kappa B activation, ABIN-1. FEBS Lett 2003; 536:135-140.
    7. Rothwarf DM, Zandi E, Natoli G, Karin M. IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex. Nature 1998; 395:297-300.
    8. Vendrell JA, Ghayad S, Ben-Larbi S et al. A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells. Oncogene 2007; 26:4656-4667.
    9. Lerebours F, Vacher S, Andrieu C et al. NF-kappa B genes have a major role in inflammatory breast cancer. BMC Cancer 2008; 8:41.
    10. Hess S, Gottfried E, Smola H et al. CD40 induces resistance to TNF-mediated apoptosis in a fibroblast cell line. Eur J Immunol 1998; 28:3594-3604.
    11. S. A.Vaziri, A. Al-Hazzouri, D. R. Grabowski et al. Sorafenib treatment of clear-cell renal cell carcinoma (CCRCC) and colorectal carcinoma (CRC) cells:Differential effects on gene expression and cell death pathways. ASCO Meeting Abstracts 2007; 25:15612.
    12. William C. Reinhold, Barry R. Zeeberg, Uma T. Shankavaram, Kohn. KW. Microarray analysis of acquired resistance to apoptosis:Improved Gene Ontology analysis through customization of categories in the GoMiner program package. Proc Amer Assoc Cancer Res 2006; 47.
    13.王爱东,黄强,陈寒春et al.凋亡相关基因tnfaip3、Enc1在人脑胶质瘤组织中的表达.中国血液流变学杂志2003:210-213.
    14. Honma K, Tsuzuki S, Nakagawa M et al. TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma. Genes Chromosomes Cancer 2008; 47:1-7.
    15. Rinaldi. A, Rancoita. PM, Bhagat. G. Array-CGH Identifies Both Common and Subtype-Specific Genomic Aberrations in Marginal Zone Lymphomas. Blood (ASH Annual Meeting Abstracts) 2008; 112: 622.
    16. Novak U, Rinaldi A, Kwee I et al. The NF-kB negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone B-cell lymphomas. Blood 2009.
    17. Laura P, Mara C, Wei Keat L, Adina G. Mutations in Multiple Genes Cause Deregulation of the NF-kappaB Pathway in Diffuse Large B-Cell Lymphoma. Blood (ASH Annual Meeting Abstracts) Nov 2008; 112:801.
    18. Bredel M, Bredel C, Juric D et al. Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to 06-alkylating agents in human glioblastomas. J Clin Oncol 2006; 24:274-287.
    19. Wang MC, Liu SX, Liu PB. Gene expression profile of multiple myeloma cell line treated by realgar. J Exp Clin Cancer Res 2006; 25:243-249.
    20. Al-Romaih K, Somers GR, Bayani J et al. Modulation by decitabine of gene expression and growth of osteosarcoma U2OS cells in vitro and in xenografts:Identification of apoptotic genes as targets for demethylation. Cancer Cell Int 2007; 7:14.
    21. Daigeler A, Chromik AM, Geisler A et al. Synergistic apoptotic effects of taurolidine and TRAIL on squamous carcinoma cells of the esophagus. Int J Oncol 2008; 32:1205-1220.
    22. Adrien D, Ludger KH, Michael CA et al. Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures. BMC Cancer 2008; 8:313.
    23. Eisele L, Klein-Hitpass L, Chatzimanolis N et al. Differential expression of drug-resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia. Acta Haematol 2007; 117:8-15.
    24. Reinhold. WC, Zeeberg. BR, Shankavaram. UT. Microarray analysis of acquired resistance to apoptosis:Improved Gene Ontology analysis through customization of categories in the GoMiner program package. Proc Amer Assoc Cancer Res 2006; 47.
    25. Longo CR, Arvelo MB, Patel VI et al. A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis. Circulation 2003; 108:1113-1118.
    26. Chng HW, Camplejohn RS, Stone MG et al. A role for A20 in tumour angiogenesis. Br. J. Cancer 91(Suppl.1)2004; S16.
    27. Chng HW, Camplejohn RS, Stone MG et al. A new role for the anti-apoptotic gene A20 in angiogenesis. Exp Cell Res 2006; 312:2897-2907.
    28. Maggio. R, Peragine. N, Messina. M, Chiaretti. S. Angiogenic Activity in IgVH Mutated and Unmutated Chronic Lymphocytic Leukemia (CLL):Indications for the Therapeutic Use of VEGF-Signaling Inhibitors. Blood (ASH Annual Meeting Abstracts) 2006; 108:2819.
    1. Nollet F, Kools P, van Roy F. Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. J Mol Biol 2000; 299: 551-572.
    2. Redies C, Vanhalst K, Roy F. delta-Protocadherins:unique structures and functions. Cell Mol Life Sci 2005; 62:2840-2852.
    3. Vanhalst K, Kools P, Staes K et al. delta-Protocadherins:a gene family expressed differentially in the mouse brain. Cell Mol Life Sci 2005; 62:1247-1259.
    10. Kuroda H, Inui M, Sugimoto K et al. Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus. Dev Biol 2002; 244:267-277.
    12. Yoshida K, Watanabe M, Kato H et al. BH-protocadherin-c, a member of the cadherin superfamily, interacts with protein phosphatase 1 alpha through its intracellular domain. FEBS Lett 1999; 460:93-98.
    13. Unterseher F, Hefele JA, Giehl K et al. Paraxial protocadherin coordinates cell polarity during convergent extension via Rho A and JNK. EMBO J 2004; 23:3259-3269.
    14. Maxwell SA, Davis GE. Biological and molecular characterization of an ECV-304-derived cell line resistant to p53-mediated apoptosis. Apoptosis 2000; 5:277-290.
    15. Yoshida K, Yoshitomo-Nakagawa K, Seki N et al. Cloning, expression analysis, and chromosomal localization of BH-protocadherin (PCDH7), a novel member of the cadherin superfamily. Genomics 1998; 49:458-461.
    16. Zhang Z, DuBois RN. Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor. Oncogene 2001; 20:4450-4456.
    17. Redies C. Cadherins in the central nervous system. Prog Neurobiol 2000; 61:611-648. 18. Heggem MA, Bradley RS. The cytoplasmic domain of Xenopus NF-protocadherin interacts with TAF1/set. Dev Cell 2003; 4:419-429.
    19. Strehl S, Glatt K, Liu QM et al. Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14. Genomics 1998; 53:81-89.
    20. Mattar P, Britz O, Johannes C et al. A screen for downstream effectors of Neurogenin2 in the embryonic neocortex. Dev Biol 2004; 273:373-389.
    21. de Tayrac M, Etcheverry A, Aubry M et al. Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression. Genes Chromosomes Cancer 2009; 48:55-68.
    22. Wilson ND, Ross LJ, Close J et al. Replication profile of PCDH11X and PCDH11Y, a gene pair located in the non-pseudoautosomal homologous region Xq21.3/Yp11.2. Chromosome Res 2007; 15: 485-498.
    23. Yang X, Chen MW, Terry S et al. A human-and male-specific protocadherin that acts through the wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells. Cancer Res 2005; 65:5263-5271.
    24. Miller EN, Fadl M, Mohamed HS et al. Y chromosome lineage-and village-specific genes on chromosomes 1p22 and 6q27 control visceral leishmaniasis in Sudan. PLoS Genet 2007; 3:e71.
    25. Yamamoto A, Amacher SL, Kim SH et al. Zebrafish paraxial protocadherin is a downstream target of spadetail involved in morphogenesis of gastrula mesoderm. Development 1998; 125:3389-3397.
    26. Kim SH, Yamamoto A, Bouwmeester T et al. The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation. Development 1998; 125: 4681-4690.
    27. Lee CH, Gumbiner BM. Disruption of gastrulation movements in Xenopus by a dominant-negative mutant for C-cadherin. Dev Biol 1995; 171:363-373.
    28. Medina A, Swain RK, Kuerner KM, Steinbeisser H. Xenopus paraxial protocadherin has signaling functions and is involved in tissue separation. EMBO J 2004; 23:3249-3258.
    29. Bray NJ, Kirov G, Owen RJ et al. Screening the human protocadherin 8 (PCDH8) gene in schizophrenia. Genes Brain Behav 2002; 1:187-191.
    30. Fidler IJ, Kim SJ, Langley RR. The role of the organ microenvironment in the biology and therapy of cancer metastasis. J Cell Biochem 2007; 101:927-936.
    31. Yu JS, Koujak S, Nagase S et al. PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene 2008; 27:4657-4665.
    32. Yu J, Cheng YY, Tao Q et al. Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer. Gastroenterology 2009; 136:640-651 e641.
    1. Yang L. Incidence and mortality of gastric cancer in China[J]. World J Gastroenterol,2006,12: 17-20.
    2. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction[J]. Anal Biochem,1987,162:156-159.
    3. Livak, K.J. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-D-elta Delta C(T)) Method. Methods,2001.25(4):p.402-8.
    4. Liu LX, Liu ZH, Jiang HC, et al. Profiling of differentially expressed genes in human gastric carcinoma by cDNA expressionarray [J]. World J Gastroenterol,2002,8(4):580-5.
    5. Hasegawa S, Furukawa Y, Li M, et al. Genome-wide analysis of gene expression in intestinal type gastric cancers using a complementary DNA microarray representing 23040 genes[J]. Cancer Res,2002, 62(23):7012-7.
    6. Mori M, Mimori K, Yoshikawa Y, et al. Analysis of the gene expression profile regarding the progression of human gastric carcinoma[J]. Surgery,2002,131(1 Suppl):39-47.
    7. Kim JM, Sohn HY, Yoon SY, et al. Identifieation of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. Clinical cancer research[J].2005, Jan 15;11(2 Pt 1):473-82.
    8. Russo G, Zegar C, Giodano A. Advantages and limitations of microarray Technology in humn cancer. Oneogene,2003, Sep 29; 22(42):6497-507.
    9. Beurtcci F, Viens P, Tagett R, et al. DNA arrays in clinical oncology:Pormises And challenges. Lab Invest.2003, Mar:83(3):305-16.
    10. Vendrell JA, Ghayad S, Ben-Larbi S, et al. A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells[J]. Oncogene,2007,26:4656-4667.
    11. Lerebours F, Vacher S, Andrieu C, et al. NF-kappa B genes have a major role in inflammatory breast cancer[J]. BMC Cancer,2008,8:41.
    12. Hess S, Gottfried E, Smola H, et al. CD40 induces resistance to TNF-mediated apoptosis in a fibroblast cell line[J]. Eur J Immunol,1998,28:3594-3604.
    13. S. A.Vaziri, A. Al-Hazzouri, D. R. Grabowski, et al. Sorafenib treatment of clear-cell renal cell carcinoma (CCRCC) and colorectal carcinoma (CRC) cells:Differential effects on gene expression and cell death pathways[J]. ASCO Meeting Abstracts,2007,25:15612.
    14. William C. Reinhold, Barry R. Zeeberg, Uma T. Shankavaram, et al. Microarray analysis of acquired resistance to apoptosis:Improved Gene Ontology analysis through customization of categories in the GoMiner program package[J]. Proc Amer Assoc Cancer Res,2006,47.
    15. Honma K, Tsuzuki S, Nakagawa M, et al. TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma[J]. Genes Chromosomes Cancer, 2008,47:1-7.
    16. Bredel M, Bredel C, Juric D, et al. Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to 06-alkylating agents in human glioblastomas[J]. J Clin Oncol,2006,24:274-287.
    17. Longo CR, Arvelo MB, Patel VI, et al. A20 protects from CD40-CD40 ligand-mediated endothelial cell activation and apoptosis[J]. Circulation,2003,108:1113-1118.
    18. Christensen H N. Role of amino acid transport and counter-transport in nutrition and metabolism [J]. Physiol Rev,1990,70:43-77.
    19. McGivan JD, Pastor-Anglada M. Regulatory and molecular aspects of mammalian amino acid transport[J]. Biochem J 1994,299 (Pt 2):321-334.
    20. Kondoh N, Imazeki N, Arai M, et al. Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues[J]. Int J Oncol, 2007,31:81-87.
    21. Bhat HK, Vadgama JV. Role of estrogen receptor in the regulation of estrogen induced amino acid transport of System A in breast cancer and other receptor positive tumor cells[J]. Int J Mol Med,2002,9: 271-279.
    22. Novak D, Quiggle F, Haafiz A. Impact of forskolin and amino acid depletion upon System A activity and SNAT expression in BeWo cells[J]. Biochimie,2006,88:39-44.
    23. Chen X, Molino C, Liu L, Gumbiner BM. Structural elements necessary for oligomerization, trafficking, and cell sorting function of paraxial protocadherin[J]. J Biol Chem,2007,282: 32128-32137.
    24. Strehl S, Glatt K, Liu QM, et al. Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14[J]. Genomics,1998,53: 81-89.
    25. de Tayrac M, Etcheverry A, Aubry M, et al. Integrative genome-wide analysis reveals a robust genomic glioblastoma signature associated with copy number driving changes in gene expression[J]. Genes Chromosomes Cancer,2009,48:55-68.
    26. Rauhala HE, Porkka KP, Tolonen TT et al. Dual-specificity phosphatase 1 and serum/gluco-corticoid-regulated kinase are downregulated in prostate cancer[J]. Int J Cancer 2005,117:738-45.
    27. Alexander DB, Goldberg GS. Transfer of biologically important molecules between cells through gap junction channels[J]. Curr Med Chem,2003,10(19):20452058.
    28.黄扬,陈丽英,高美钦.胃癌和胃癌前病变Cx43、PCNA的表达及意义[J].福建医科大学学报,2002,36(4):382384.
    29.辛小燕,马向东,陈必良,等.Cx43蛋白在宫颈癌细胞中的表达及其对细胞通讯功能的影响[J].第四军医大学学报,2000,21(3):369371.
    30.夏之柏,浦佩玉,黄强,等.连接蛋白基因Cx43抑制胶质瘤细胞增殖及其机理的初步探讨[J].中华肿瘤杂志,2003,25(1):48.
    31. 陈华,王东跃,李小六,等.糖基转移酶抑制剂研究进展[J].有机化学,2009,29(5):703-715.
    32. Lee SM, Tsui SK, Chan KK, et al. Chromosomal mapping, tissue distribution and cDNA sequence of four-and-a-half LIM domain protein 1 (FHL1) [J]. Gene,1998,216:163-170.
    33.郭俊唐,周乃康,叶棋浓,等.FHL家族与肿瘤的关系[J].生物技术通讯,2008;19(3):23-24.
    34. Sakashita K, Mimori K, Tanaka F, et al. Clinical significance of loss of Fhll expression in human gastric cancer[J]. Ann Surg Oncol,2008,15:2293-2300.
    35. Liao F, Rabin RL, Yannelli JR, Koniaris LG, Vanguri P, Farber JM. Human Mig chemokine: biochemical and functional characterization [J]. J Exp Med,1995, Nov 1,182(5):1301-14.
    36.路慧丽,俞眉,韩伟,等.趋化因子CXCL9/Mig的研究进展[J].中国生物工程杂志,2006,26(10):59-63.
    1. Kononen J, Bubendorf L, Kallioniemi A, et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens[J]. Nat Med,1998,4(7):844-7.
    2. Zheng HC, Tsuneyama K, Takahashi H, et al. Aberrant Pim-3 expression is involved in gastric adenoma-adenocarcinoma sequence and cancer progression[J]. J Cancer Res Clin Oncol,2008 Apr,134(4):481-8.
    3. Morales Espinosa Mdel R, Delgado Sapien G, Cravioto A. The use of microarrays for studying the pathogenesis of Helicobacter pylori[J]. Rev Latinoam Microbiol,2003 Jan-Jun,45(1-2):24-9.
    4. Lee OJ, Hong SM, Razvi MH, et al. Expression of calcium-binding proteins S100A2 and S100A4 in Barrett's adenocarcinomas[J]. Neoplasia,2006 Oct,8(10):843-50.
    5. Lam-Himlin DM, Daniels JA, Gayyed MF, et al. The hippo pathway in human upper gastro-intestinal dysplasia and carcinoma:a novel oncogenic pathway[J]. Int J Gastrointest Cancer,2006, 37(4):103-9.
    6. Li XH, Zheng HC, Wang ZG, et al. The clinicopathological and prognostic significance of M-UC-1 expression in Japanese gastric carcinomas:an immunohistochemical study of tissue micro-arrays[J]. Anticancer Res,2008 Mar-Apr,28(2A):1061-7.Links.
    7. Guan-Zhen Y, Ying C, Can-Rong N, et al. Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer[J].Int J Exp Pathol,2007 Jun,88(3):175-83.
    8. Li M, Liu W, Zhu YF, et al. Correlation of COX-2 and K-ras expression to clinical outcome in gastric cancer[J]. Acta Oncol,2006,45(8):1115-9.
    9. Yu M, Zheng H, Tsuneyama K, et al. Paradoxical expression of maspin in gastric carcinomas: correlation with carcinogenesis and progression[J]. Hum Pathol,2007 Aug,38(8):1248-55. Epub 2007 May 8.
    10. Tsai WC, Jin JS, Chang WK, et al. Association of cortactin and fascin-1 expression in gastric adenocarcinoma:correlation with clinicopathological parameters[J]. J Histochem Cytochem,2007 Sep,55(9):955-62. Epub 2007 May 17.
    11. Zheng H, Takahashi H, et al. Pathobiological characteristics of intestinal and diffuse-type gastric carcinoma in Japan:an immunostaining study on the tissue microarray[J].J Clin Pathol,2007 Mar,60(3):273-7. Epub 2006 May 19.
    12. Went P, Vasei M, Bubendorf L, et al. Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers[J]. Br J Cancer, 2006 Jan 16,94(1):128-35.
    13. Sun Y, Chen XY, et al. Differential caspase-3 expression in noncancerous, permalignant and cancer tissues of stomach and its clinical implication[J]. Cancer Detect Prev,2006,30(2):168-73.
    14. Goodwin AC, Jadallah S, Toubaji A, et al. Increased spermine oxidase expression in human prostate cancer and prostatic intraepithelial neoplasia tissues[J]. Prostate.2008 May 15,68(7):766-72.
    15. Leys CM, Nomura S, et al. Expression and prognostic significance of prothymosin-alpha and ERp57 in human gastric cancer[J]. Surgery.2007 Jan,141(1):41-50.
    16. Kondoh N, Imazeki N, Arai M et al. Activation of a system A amino acid transporter, ATA1 /SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues[J]. Int J Oncol,2007,31:
    1. Sugawara M, Nakanishi T, Fei YJ, et al. Cloning of an amino acid transporter with functional characteristics and tissue expression pattern identical to that of system A[J]. J Biol Chem,2000,275: 16473-16477.
    2. Kondoh N, Imazeki N, Arai M et al. Activation of a system A amino acid transporter, ATA1/SLC38A1, in human hepatocellular carcinoma and preneoplastic liver tissues[J]. Int J Oncol, 2007,31:81-87.
    3. Christensen HN. Role of amino acid transport and countertransport in nutrition and metabolism[J]. Physiol Rev,1990,70:43-77.
    4. Seow HF, Broer S, Broer A, et al. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19[J]. Nat Genet,2004,36:1003-1007.
    5. Hatanaka T, Hatanaka Y, Tsuchida J, et al. Amino acid transporter ATA2 is stored at the trans-Golgi network and released by insulin stimulus in adipocytes[J]. J Biol Chem,2006,281: 39273-39284.
    6. Kim DK, Kanai Y, Choi HW, et al. Characterization of the system L amino acid transporter in T24 human bladder carcinoma cells[J]. Biochim Biophys Acta,2002,1565:112-121.
    7. Lin J, Raoof DA, Thomas DG et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma[J]. Neoplasia,2004,6:74-84.
    8. Campbell WA, Thompson NL. Overexpression of LAT1/CD98 light chain is sufficient to increase system L-amino acid transport activity in mouse hepatocytes but not fibroblasts[J]. J Biol Chem,2001, 276:16877-16884.
    9. Kim DK, Ahn SG, Park JC, et al. Expression of L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in oral squamous cell carcinoma and its precusor lesions[J]. Anticancer Res,2004, 24:1671-1675.
    10. Bhat HK, Vadgama JV. Role of estrogen receptor in the regulation of estrogen induced amino acid transport of System A in breast cancer and other receptor positive tumor cells[J]. Int J Mol Med,2002,9: 271-279.
    11. Novak D, Quiggle F, Haafiz A. Impact of forskolin and amino acid depletion upon System A activity and SNAT expression in BeWo cells[J]. Biochimie,2006,88:39-44.
    12. Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J]. Nature,1998,391:806-811.
    13. Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature,2001,411:494-498.
    14. Chakraborty C. Potentiality of small interfering RNAs (siRNA) as recent therapeutic targets for gene-silencing[J]. Curr Drug Targets,2007,8:469-482.
    15. Rubinson DA, Dillon CP, Kwiatkowski AV, et al. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference[J]. Nat Genet, 2003,33:401-406.
    16. Brummelkamp TR, Bernards R, Agami R. A system for stable expression of short interfering RNAs in mammalian cells[J]. Science,2002,296:550-553
    17. Wu Y, Shen D, Chen Z, et al. Taxol induced apoptosis regulates amino acid transport in breast cancer cells[J]. Apoptosis,2007,12:593-612.
    18. NakanishiK, MatsuoH, KanaiY, et al. LAT1 expressionin normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung[J]. Virchows Arch,2006,448(2):142-50.
    19. Rajan DP, KekudaR, HuangW, et al. Cloning and functional characterization of a Na+ -independent, broad-specific neutral amino acid transporter from mammalian intestine[J]. Biochim Biophys Acta,2000, 1463(1):6-14.
    20. Kim SG, Kim HH, Kim HK, et al. Diferential expression and functional characterization of system L amino acid transporters in human normal osteoblast cells and osteogenic sarcoma cells[J]. Anticancer Res,2006,26(3A):1989-96.
    21. Simmons, Willis TA, Koh AS, Clarkson TW, et al. Transport of a neurotoxicant by molecular mimicry:the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter(LAT)1 and LAT2[J]. Biochem J,2002,367(Pt 1):239-46.
    22. Lin J, Raoof DA, Thomas DG, et al. L-type amino acid transporter-1 overexpression and melphalan sensitivity in Barrett's adenocarcinoma[J]. Neoplasia,2004,6(1):74-84.
    23. Yoon JH, Kim IJ, Kiln H, et al. Amino acidt ransport system L is differently expressed in human norma oral keratinocytes And human oral cancer cells[J]. Cacer Lett,2005,222(2):237-45.
    24. Yoon JH, Kim YB, Kim MS, et al. Expression and functional characterization of the system L amino acid transporter in KB human oral epidermoid carcinoma cells[J]. Cancer Lett,2004,205(2): 215-26.
    25. Baniasadi S, Chairoungdua A, Iribe Y, et al. Gene expression profiles in T24 human bladder carcinoma cells by inhibiting an L-type amino acid transporter, LAT1[J]. Arch Pharm Res,2007, 30(4):444-52.
    26. Nawashiro H, Otani N, Shinomiya N, et al. L-type amino acid transporter 1 as a potential molecular target in human astrocytic tumors[J]. Int J Cancer,2006,119(3):484-92.
    27.高进,章静波.癌的侵袭与转移-基础与临床[M].北京:科学出版社,2003.

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