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博碩士論文 etd-0816105-184002 詳細資訊
Title page for etd-0816105-184002
論文名稱
Title
蛋白質體學之大腸直腸癌差異性蛋白質表現分析
Proteomic analysis of differentially expressed proteins in colorectal cancer
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
171
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2005-07-15
繳交日期
Date of Submission
2005-08-16
關鍵字
Keywords
二維電泳法、質譜儀、大腸直腸癌、蛋白質體學
SW620, CD2AP, 2D, SW480, Oxaliplatin, MALDI-TOF, HT-29, Proteomics, 5-Fu, PTTG1
統計
Statistics
本論文已被瀏覽 5694 次,被下載 5336
The thesis/dissertation has been browsed 5694 times, has been downloaded 5336 times.
中文摘要
本實驗經由收集外科手術所取得的大腸直腸癌癌化組織與正常組織,來進行蛋白質差異性表現研究,收集的癌症檢體其癌化程度分別有T1~T4時期等樣品(依TNM系統分類),我們利用二維電泳法與質譜鑑定技術來分析並經由統計分析定義出十八種差異性表現的蛋白質。本實驗結果顯示有十三種在腫瘤組織中會表現量上升的差異性蛋白質,分別是Keratin 8、Protein disuflde isomerase A3 precursor、 Keratin 18、Fractalkine precursor、LDH-B、 Tropomyosin alpha 4 chain、Tropomyosin alpha 3 chain、chloride intracellular channel protein 1、PTTG1(Pituitary tumor-transforming protein 1)、
Abstract
We gathered normal and colorectal cancer tissues from 18 patients after tumor surgery. The tumor tissues represent caner stages from T1 to T4 (TNM system).Two-dimensional electrophoresis and MALDI-TOF techniques were utilized to identify the differentially expressed proteins. Our studies showed that there are about 18 differentially expressed proteins in normal and tumor tissues (p<0.05) which 13 proteins increased in tumor were Keratin 8, Protein disuflde isomerase A3 precursor, Keratin 18, Fractalkine precursor, LDH-B, Tropomyosin alpha 4 chain, Tropomyosin alpha 3 chain, chloride intracellular channel protein 1, PTTG1(Pituitary tumor-transforming protein 1),
目次 Table of Contents
Contents

中文摘要……………………………………………………………1
英文摘要…………………………………………………………… 2
英文縮寫表………………………………………………………… 3

壹、前言…………………………………………………………………5
一.大腸直腸癌之蛋白質分析與重要性………………………………5
1.1大腸直腸位置與解剖圖……………………………………………6
1.2大腸直腸癌好發區域………………………………………… 6
1.3病理特性與分期……………………………………………………7
1.4大腸直腸癌之病因學………………………………………………9
1.4.1偶發性大腸直腸癌………………………………………………10
1.4.2家族性多發腺瘤性息肉(Familial Adenomatous Polyposis,FAP)…12
1.4.3遺傳性非息肉性大腸直腸癌
(Hereditary Nonpolyposis Colorectal Cancer,HNPCC)…………………14
1.5篩檢與治療…………………………………………………………15
1.5.1化學治療…………………………………………………………16
二.蛋白質體學(Proteomics)及其定義………………………………17
三.基質輔助雷射脫附游離質譜分析法(MALDI-TOF/MS)……………18
(1)直線型TOF…………………………………………………………19
(2)反射型TOF…………………………………………………………19
四.蛋白質體學在大腸直腸癌上的應用(Proteomics of study colorectal cancer)…21
五.研究目標…………………………………………………………22

貳、實驗流程(Experiment flowchart)……………………………23

參、材料與方法(Materials and Methods)…………………… 27
一.大腸直腸組織樣品處理……………………………………………27
1.檢體來源………………………………………………………… 27
2.大腸直腸癌病人血液與組織蛋白質萃取…………………………27
2.1血液蛋白質萃取…………………………………………………27
2.2組織蛋白質萃取……………………………………………………27
2.3大腸直腸癌細胞株SW480、SW620、HT-29之蛋白質萃取………28
2.4 TCA/Actone沉澱…………………………………………………28
2.5蛋白質定量…………………………………………………………28
3.二維電泳法……………………………………………………… 29
3.1 Isoeletric focusing electrophoresis(聚電焦電泳)………29
3.2 Immobiline Drystrip Equilibration…………………………29
3.3 Sodiumdodecylsufate Polyacrylamide Gel Electrophoresis(SDS-PAGE)(聚丙烯&#37244;胺膠體電泳)…………………………………30
3.4 Silver stain 銀離子染色………………………………………31
3.5 Coomassie brilliant blue R-250 stain……………………31
4.Gel imaging analysis 膠體影像分析及統計分析……………32
5.In gel digestion…………………………………………………32
5.1清洗(Washing)……………………………………………………32
5.2 Coomassie brilliant blue R-250 stain退染………………32
5.3 Reduction/Alkylation…………………………………………33
5.4 Digestion/Extraction…………………………………………33
5.5 MALDI-TOF質譜操作………………………………………………33
5.6 PSD(Post Source Decay)(Tandem TOF/TOF MS)操作…………34
5.7使用ProteinProspector之MS-Fit來辨認未知的蛋白質………34
6.西方墨點電泳法(Western blotting)……………………………34
6.1 COX2蛋白質表現測試……………………………………………35
6.2 CD2AP蛋白質表現測試……………………………………………36
6.3 PTTG1蛋白質表現測試…………………………………………36
二.大腸直腸癌RNA萃取………………………………………………36
1.Total RNA抽取……………………………………………………36
2.將mRNA反轉錄成cDNA……………………………………………37
3. PCR聚合&#37238;連鎖反應………………………………………………37
4. PCR引子之設計……………………………………………………38
三.大腸直腸癌細胞株SW480、SW620、HT-29之培養與處理………39
1.材料…………………………………………………………………39
2.冷凍細胞解凍程序…………………………………………………39
3.細胞繼代培養(subculture)與細胞計數…………………………40
4.細胞冷凍程序………………………………………………………40
5.MTT抗癌活性測試…………………………………………………41
5.1細胞計數與種植(Seeding)………………………………………41
5.2加藥(Treatment 5-Fu or Oxaliplatin anti-cancer drugs)41
5.3加入MTT…………………………………………………………41
5.4加入DMSO……………………………………………………………41
5.5 ELISA reader……………………………………………………42



肆、實驗結果(Results)……………………………………………43
一.大腸直腸癌檢體之分析結果……………………………………43
二.二維電泳膠片之分析結果………………………………………43
2.1大腸直腸癌正常組織與癌化組織之二維電泳膠片分析………43
2.2軟體比對分析與統計差異性與非差異性之二維電泳膠片上之spot...................................................44
三.MALDI-TOF質譜分析與蛋白質資料庫比對……………………45
3.1 MS質譜分析……………………………………………………45
3.2差異性蛋白質身份鑑定………………………………………45
四.差異性蛋白質伴隨癌化過程中之各個時期表現…………………46
4.1伴隨在癌化過程表現上升的差異性蛋白質………………………46
4.2隨著癌化過程表現下降的差異性蛋白質…………………………48
五.Tandem(TOF/TOF) Mass spectrometry質譜分析結果…………49
六.大腸直腸癌組織RT-PCR結果分析…………………………………50
(A) Keratin在組織中RT-PCR之表現…………………………… 50
(B) PTTG1在組織中RT-PCR之表現……………………………… 50
(C) RAB11A在組織中RT-PCR之表現………………………………50
(D) CD2AP在組織中RT-PCR之表現…………………………………50
(E) VAMP-B/C在組織中RT-PCR之表現………………………………51
七.大腸直腸癌組織之西方點墨法結果分析(Western blotting)…51
7.1 COX2(Ptgs2)蛋白質表現之結果…………………………………51
7.2 CD2AP蛋白質表現之結果…………………………………………51
八.大腸直腸癌癌細胞株抗癌活性測試………………………………51
8.1利用抗癌藥5-Fu treatment SW480、SW620、HT-29等大腸直腸癌細胞株後期存活率之結果……………………………………………51
8.2利用抗癌藥Oxaliplatin treatment SW480、SW620、HT-29等大腸直腸癌細胞株後期存活率之結果…………………………………53
九.大腸直腸癌細胞株之二維電泳圖結果分析………………………54
十.大腸直腸癌細胞株之CD2AP、PTTG1之western blotting結果分析.......................................................54

伍、實驗討論(Discussion).................................56
一.大腸直腸癌組織之二維電泳實驗討論……………………………56
二.差異性蛋白質之RT-PCR實驗討論…………………………………57
2.1 PTTG1………………………………………………………………58
2.2 RAB11A……………………………………………………………58
2.3 CD2AP………………………………………………………………58
2.4 VAMP-B/C…………………………………………………………58
三.大腸直腸癌組織差異性蛋白質之western blot實驗討論………58
四.大腸直腸癌細胞株SW480、SW620、HT-29利用藥物處理後之存活率實驗討論...............................................59
五.大腸直腸癌細胞株差異性蛋白質CD2AP與PTTG1之western blot實驗討論...................................................59
六.差異性蛋白質之介紹與討論………………………………………61
6.1 PTTG1……………………………………………………………62
6.2 CD2AP……………………………………………………………64
6.3 Tropomyosin……………………………………………………66
6.4 Alpha-1-antitrypsin…………………………………………67
6.5 RAB11A…………………………………………………………68
6.6 VAMP-B/C………………………………………………………68
6.7 StARD5…………………………………………………………69
6.8 Fractalkine (CX3CL1)………………………………………70
6.9 CLIC1(NCC27)…………………………………………………71
6.10 Peroxiredoxin 2……………………………………………71

陸、結論與展望………………………………………………………73

柒、參考文獻(Reference)……………………………………………74

捌.圖與表(Figures & Tables Contents)…………………………77
文獻探討(Literature Review)
圖一.大腸直腸位置與解剖圖…………………………………………6
圖二.大腸腸道剖面圖…………………………………………………7
圖三. Molecular events that characterize the transition to adenocarcinoma..........................................12
圖四. The Wnt signaling pathway…………………………………14
圖五.直線型TOF與反射型TOF…………………………………………20
表一. AJCC/UICC TNM. Definition*…………………………………8
表二. AJCC/UICC Stage Groupings…………………………………8
材料與方法(Materials and Methods)
表三.經由NCBI Homepage所設計出來之RT-PCR引子………………37
實驗結果(Results)
表五.大腸直腸癌病患基本資料與臨床病徵一覽表…………………82
表六.大腸直腸癌蛋白質差異性表現一覽表…………………………83
表七.大腸直腸癌蛋白質未差異性表現一覽表………………………84
表八.大腸直腸癌隨癌化後表現增加之差異性蛋白質身分鑑定一覽表.......................................................85
表九.大腸直腸癌隨癌化後表現減少之差異性蛋白質身分鑑定一覽表.......................................................86
表十.大腸直腸癌隨癌化後無差異性表現之蛋白質身分鑑定一覽表.......................................................87
圖十. Master gel (Analytical gel)………………………………91
圖十一.~圖十五.大腸直腸癌差異性蛋白質表現之二維電泳圖……92
圖十六.大腸直腸癌癌化後差異性蛋白質表現增加之相對百分比關係圖………………………………………………………………………97
圖十七.大腸直腸癌癌化後差異性蛋白質表現減少之相對百分比關係圖………………………………………………………………………98
圖十八.~圖三十五.差異性蛋白質在大腸直腸癌組織中隨著癌化之不同時期表現趨勢圖……………………………………………………99
圖三十六.~圖三十八.MS/MS(PSD)質譜分析圖……………………108
圖三十九.~圖四十.RT-PCR之結果分析……………………………111
圖四十一. Western blotting analysis of COX2………………113
圖四十二. Western blotting analysis of CD2AP……………114
圖四十三.~圖四十四.大腸直腸癌細胞株加入5-Fu抗癌藥後細胞相對存活率趨勢圖…………………………………………………………115
圖四十五.~四十六.大腸直腸癌細胞株加入Oxaliplatin抗癌藥後細胞相對存活率趨勢圖…………………………………………………117
圖四十七.~五十二.2-D electrophoresis profile of human colorectal cancer cell lines of SW480、SW620 and HT-29…119
圖五十三.大腸直腸癌細胞株之差異性蛋白質CD2AP與PTTG1之Western bolting analysis…………………………………………125

實驗討論(Discussion)
圖六. Model of regulation of mitosis and G1 by APC-dependent cyclin proteolysis……………………………………63
圖七.Regulation of sister chromatid separation by the APC.....................................................63
圖八.CD2AP complex binding EGF…………………………………65
圖九.CD2AP complex binding VEGFR………………………………65

附錄(Appendix)………………………………………………126
圖五十四.~七十一.2-D electrophoresis profile of human colorectal cancer patient………………………………………127
圖七十二. 2-D electrophoresis profile of human colorectal cancer cell line of SW 480 and SW620………………………145
附圖一.~附圖十八.差異性蛋白質經過Trypsin分解片段的質譜分....................................................146
附表一.~附表十八.差異性蛋白質之MS peaks match coverage percentage............................................146
參考文獻 References
Alessandro, R., Belluco, C., and Kohn, E. C. (2005). Proteomic approaches in colon cancer: promising tools for new cancer markers and drug target discovery. Clin Colorectal Cancer 4, 396-402.

Bae, Y. S., Sung, J. Y., Kim, O. S., Kim, Y. J., Hur, K. C., Kazlauskas, A., and Rhee, S. G. (2000). Platelet-derived growth factor-induced H(2)O(2) production requires the activation of phosphatidylinositol 3-kinase. J Biol Chem 275, 10527-10531.

Bazan, J. F., Bacon, K. B., Hardiman, G., Wang, W., Soo, K., Rossi, D., Greaves, D. R., Zlotnik, A., and Schall, T. J. (1997). A new class of membrane-bound chemokine with a CX3C motif. Nature 385, 640-644.

Behrens, J. (2000). Control of beta-catenin signaling in tumor development. Ann N Y Acad Sci 910, 21-33; discussion 33-25.

Bhattacharjee, A., Richards, W. G., Staunton, J., Li, C., Monti, S., Vasa, P., Ladd, C., Beheshti, J., Bueno, R., Gillette, M., et al. (2001). Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci U S A 98, 13790-13795.

Boyer, J., McLean, E. G., Aroori, S., Wilson, P., McCulla, A., Carey, P. D., Longley, D. B., and Johnston, P. G. (2004). Characterization of p53 wild-type and null isogenic colorectal cancer cell lines resistant to 5-fluorouracil, oxaliplatin, and irinotecan. Clin Cancer Res 10, 2158-2167.

Brunagel, G., Schoen, R. E., Bauer, A. J., Vietmeier, B. N., and Getzenberg, R. H. (2002a). Nuclear matrix protein alterations associated with colon cancer metastasis to the liver. Clin Cancer Res 8, 3039-3045.

Brunagel, G., Schoen, R. E., and Getzenberg, R. H. (2004). Colon cancer specific nuclear matrix protein alterations in human colonic adenomatous polyps. J Cell Biochem 91, 365-374.

Brunagel, G., Vietmeier, B. N., Bauer, A. J., Schoen, R. E., and Getzenberg, R. H. (2002b). Identification of nuclear matrix protein alterations associated with human colon cancer. Cancer Res 62, 2437-2442.


Buyru, N., Budak, M., Yazici, H., and Dalay, N. (2003). p53 gene mutations are rare in human papillomavirus-associated colon cancer. Oncol Rep 10, 2089-2092.

Choi, M. H., Lee, I. K., Kim, G. W., Kim, B. U., Han, Y. H., Yu, D. Y., Park, H. S., Kim, K. Y., Lee, J. S., Choi, C., et al. (2005). Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature 435, 347-353.

Combadiere, C., Salzwedel, K., Smith, E. D., Tiffany, H. L., Berger, E. A., and Murphy, P. M. (1998). Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1. J Biol Chem 273, 23799-23804.

Compton, C. C., and Greene, F. L. (2004). The staging of colorectal cancer: 2004 and beyond. CA Cancer J Clin 54, 295-308.

Dulhunty, A., Gage, P., Curtis, S., Chelvanayagam, G., and Board, P. (2001). The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator. J Biol Chem 276, 3319-3323.

Fong, A. M., Alam, S. M., Imai, T., Haribabu, B., and Patel, D. D. (2002). CX3CR1 tyrosine sulfation enhances fractalkine-induced cell adhesion. J Biol Chem 277, 19418-19423.

Friedman, D. B., Hill, S., Keller, J. W., Merchant, N. B., Levy, S. E., Coffey, R. J., and Caprioli, R. M. (2004). Proteome analysis of human colon cancer by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics 4, 793-811.

Friesel, R. E., and Maciag, T. (1995). Molecular mechanisms of angiogenesis: fibroblast growth factor signal transduction. Faseb J 9, 919-925.

Grunkemeyer, J. A., Kwoh, C., Huber, T. B., and Shaw, A. S. (2005). CD2AP expression in podocytes rescues lethality of CD2AP deficiency. J Biol Chem.

Harbottle, A., Daly, A. K., Atherton, K., and Campbell, F. C. (2001). Role of glutathione S-transferase P1, P-glycoprotein and multidrug resistance-associated protein 1 in acquired doxorubicin resistance. Int J Cancer 92, 777-783.

Harrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998). Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci U S A 95, 10896-10901.
Heaney, A. P., Singson, R., McCabe, C. J., Nelson, V., Nakashima, M., and Melmed, S. (2000). Expression of pituitary-tumour transforming gene in colorectal tumours. Lancet 355, 716-719.

Huelsken, J., and Behrens, J. (2002). The Wnt signalling pathway. J Cell Sci 115, 3977-3978.

Hundhausen, C., Misztela, D., Berkhout, T. A., Broadway, N., Saftig, P., Reiss, K., Hartmann, D., Fahrenholz, F., Postina, R., Matthews, V., et al. (2003). The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood 102, 1186-1195.

Imai, T., Hieshima, K., Haskell, C., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T. J., and Yoshie, O. (1997). Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91, 521-530.

Ishikawa, H., Heaney, A. P., Yu, R., Horwitz, G. A., and Melmed, S. (2001). Human pituitary tumor-transforming gene induces angiogenesis. J Clin Endocrinol Metab 86, 867-874.

Jacob, S., and Praz, F. (2002). DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie 84, 27-47.

Junutula, J. R., Schonteich, E., Wilson, G. M., Peden, A. A., Scheller, R. H., and Prekeris, R. (2004). Molecular characterization of Rab11 interactions with members of the family of Rab11-interacting proteins. J Biol Chem 279, 33430-33437.

Kamei, T., Matozaki, T., and Takai, Y. (1999). [Mechanisms of cell adhesion and migration]. Gan To Kagaku Ryoho 26, 1359-1366.

Kang, S. W., Chae, H. Z., Seo, M. S., Kim, K., Baines, I. C., and Rhee, S. G. (1998). Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J Biol Chem 273, 6297-6302.

Kataoka, H., Itoh, H., and Koono, M. (2002). Emerging multifunctional aspects of cellular serine proteinase inhibitors in tumor progression and tissue regeneration. Pathol Int 52, 89-102.

Kerr, D. (2003). Clinical development of gene therapy for colorectal cancer. Nat Rev Cancer 3, 615-622.

Kho, P. S., Wang, Z., Zhuang, L., Li, Y., Chew, J. L., Ng, H. H., Liu, E. T., and Yu, Q. (2004). p53-regulated transcriptional program associated with genotoxic stress-induced apoptosis. J Biol Chem 279, 21183-21192.

Kinzler, K. W., and Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell 87, 159-170.

Kobayashi, S., Sawano, A., Nojima, Y., Shibuya, M., and Maru, Y. (2004). The c-Cbl/CD2AP complex regulates VEGF-induced endocytosis and degradation of Flt-1 (VEGFR-1). Faseb J 18, 929-931.

Komarova, N. L., and Wang, L. (2004). Initiation of colorectal cancer: where do the two hits hit? Cell Cycle 3, 1558-1565.

Kondo, T., Seike, M., Mori, Y., Fujii, K., Yamada, T., and Hirohashi, S. (2003). Application of sensitive fluorescent dyes in linkage of laser microdissection and two-dimensional gel electrophoresis as a cancer proteomic study tool. Proteomics 3, 1758-1766.

Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., Vogelstein, B., and Clevers, H. (1997). Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science 275, 1784-1787.

Le Naour, F. (2001). Contribution of proteomics to tumor immunology. Proteomics 1, 1295-1302.

Lee, K. H., Dinner, A. R., Tu, C., Campi, G., Raychaudhuri, S., Varma, R., Sims, T. N., Burack, W. R., Wu, H., Wang, J., et al. (2003). The immunological synapse balances T cell receptor signaling and degradation. Science 302, 1218-1222.

Lexander, H., Franzen, B., Hirschberg, D., Becker, S., Hellstrom, M., Bergman, T., Jornvall, H., Auer, G., and Egevad, L. (2005). Differential protein expression in anatomical zones of the prostate. Proteomics 5, 2570-2576.

Li, X., Meriane, M., Triki, I., Shekarabi, M., Kennedy, T. E., Larose, L., and Lamarche-Vane, N. (2002). The adaptor protein Nck-1 couples the netrin-1 receptor DCC (deleted in colorectal cancer) to the activation of the small GTPase Rac1 through an atypical mechanism. J Biol Chem 277, 37788-37797.


Lin, J. L., Geng, X., Bhattacharya, S. D., Yu, J. R., Reiter, R. S., Sastri, B., Glazier, K. D., Mirza, Z. K., Wang, K. K., Amenta, P. S., et al. (2002). Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer. Gastroenterology 123, 152-162.

Longley, D. B., Allen, W. L., McDermott, U., Wilson, T. R., Latif, T., Boyer, J., Lynch, M., and Johnston, P. G. (2004). The roles of thymidylate synthase and p53 in regulating Fas-mediated apoptosis in response to antimetabolites. Clin Cancer Res 10, 3562-3571.

Loukola, A., Eklin, K., Laiho, P., Salovaara, R., Kristo, P., Jarvinen, H., Mecklin, J. P., Launonen, V., and Aaltonen, L. A. (2001). Microsatellite marker analysis in screening for hereditary nonpolyposis colorectal cancer (HNPCC). Cancer Res 61, 4545-4549.

Lynch, D. K., Winata, S. C., Lyons, R. J., Hughes, W. E., Lehrbach, G. M., Wasinger, V., Corthals, G., Cordwell, S., and Daly, R. J. (2003). A Cortactin-CD2-associated protein (CD2AP) complex provides a novel link between epidermal growth factor receptor endocytosis and the actin cytoskeleton. J Biol Chem 278, 21805-21813.

Mazelin, L., Bernet, A., Bonod-Bidaud, C., Pays, L., Arnaud, S., Gespach, C., Bredesen, D. E., Scoazec, J. Y., and Mehlen, P. (2004). Netrin-1 controls colorectal tumorigenesis by regulating apoptosis. Nature 431, 80-84.

Nishimura, Y., Hayashi, M., Inada, H., and Tanaka, T. (1999). Molecular cloning and characterization of mammalian homologues of vesicle-associated membrane protein-associated (VAMP-associated) proteins. Biochem Biophys Res Commun 254, 21-26.

Noh, D. Y., Ahn, S. J., Lee, R. A., Kim, S. W., Park, I. A., and Chae, H. Z. (2001). Overexpression of peroxiredoxin in human breast cancer. Anticancer Res 21, 2085-2090.
Ogbagabriel, S., Fernando, M., Waldman, F. M., Bose, S., and Heaney, A. P. (2005). Securin is overexpressed in breast cancer. Mod Pathol 18, 985-990.

Ohta, M., Tanaka, F., Yamaguchi, H., Sadanaga, N., Inoue, H., and Mori, M. (2005). The high expression of Fractalkine results in a better prognosis for colorectal cancer patients. Int J Oncol 26, 41-47.

Pan, Y., Lloyd, C., Zhou, H., Dolich, S., Deeds, J., Gonzalo, J. A., Vath, J., Gosselin, M., Ma, J., Dussault, B., et al. (1997). Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation. Nature 387, 611-617.

Pandey, A., and Mann, M. (2000). Proteomics to study genes and genomes. Nature 405, 837-846.

Pei, L., and Melmed, S. (1997). Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol 11, 433-441.

Petrelli, A., Gilestro, G. F., Lanzardo, S., Comoglio, P. M., Migone, N., and Giordano, S. (2002). The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met. Nature 416, 187-190.

Polakis, P. (1997). The adenomatous polyposis coli (APC) tumor suppressor. Biochim Biophys Acta 1332, F127-147.

Ponting, C. P., and Aravind, L. (1999). START: a lipid-binding domain in StAR, HD-ZIP and signalling proteins. Trends Biochem Sci 24, 130-132.

Ramaswamy, S., Ross, K. N., Lander, E. S., and Golub, T. R. (2003). A molecular signature of metastasis in primary solid tumors. Nat Genet 33, 49-54.

Reboud-Ravaux, M. (2001). [Elastase inhibitors]. J Soc Biol 195, 143-150.
Roblick, U. J., Hirschberg, D., Habermann, J. K., Palmberg, C., Becker, S., Kruger, S., Gustafsson, M., Bruch, H. P., Franzen, B., Ried, T., et al. (2004). Sequential proteome alterations during genesis and progression of colon cancer. Cell Mol Life Sci 61, 1246-1255.

Rodriguez-Agudo, D., Ren, S., Hylemon, P. B., Redford, K., Natarajan, R., Del Castillo, A., Gil, G., and Pandak, W. M. (2005). Human StarD5, a cytosolic StAR-related lipid binding protein. J Lipid Res.

Sano, H., Kawahito, Y., Wilder, R. L., Hashiramoto, A., Mukai, S., Asai, K., Kimura, S., Kato, H., Kondo, M., and Hla, T. (1995). Expression of cyclooxygenase-1 and -2 in human colorectal cancer. Cancer Res 55, 3785-3789.

Shih, N. Y., Li, J., Karpitskii, V., Nguyen, A., Dustin, M. L., Kanagawa, O., Miner, J. H., and Shaw, A. S. (1999). Congenital nephrotic syndrome in mice lacking CD2-associated protein. Science 286, 312-315.




Skvortsov, S., Sarg, B., Loeffler-Ragg, J., Skvortsova, I., Lindner, H., Werner Ott, H., Lukas, P., Illmensee, K., and Zwierzina, H. (2004). Different proteome pattern of epidermal growth factor receptor-positive colorectal cancer cell lines that are responsive and nonresponsive to C225 antibody treatment. Mol Cancer Ther 3, 1551-1558.

Slattery, M. L., Curtin, K., Anderson, K., Ma, K. N., Edwards, S., Leppert, M., Potter, J., Schaffer, D., and Samowitz, W. S. (2000). Associations between dietary intake and Ki-ras mutations in colon tumors: a population-based study. Cancer Res 60, 6935-6941.

Soccio, R. E., Adams, R. M., Maxwell, K. N., and Breslow, J. L. (2005). Differential gene regulation of StarD4 and StarD5 cholesterol transfer proteins. Activation of StarD4 by sterol regulatory element-binding protein-2 and StarD5 by endoplasmic reticulum stress. J Biol Chem 280, 19410-19418.

Soccio, R. E., and Breslow, J. L. (2003). StAR-related lipid transfer (START) proteins: mediators of intracellular lipid metabolism. J Biol Chem 278, 22183-22186.

Solbach, C., Roller, M., Peters, S., Nicoletti, M., Kaufmann, M., and Knecht, R. (2005). Pituitary tumor-transforming gene (PTTG): a novel target for anti-tumor therapy. Anticancer Res 25, 121-125.

Somsel Rodman, J., and Wandinger-Ness, A. (2000). Rab GTPases coordinate endocytosis. J Cell Sci 113 Pt 2, 183-192.

Soubeyran, P., Kowanetz, K., Szymkiewicz, I., Langdon, W. Y., and Dikic, I. (2002). Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors. Nature 416, 183-187.

Tokunaga, E., Oda, S., Fukushima, M., Maehara, Y., and Sugimachi, K. (2000). Differential growth inhibition by 5-fluorouracil in human colorectal carcinoma cell lines. Eur J Cancer 36, 1998-2006.

Tomonaga, T., Matsushita, K., Yamaguchi, S., Oh-Ishi, M., Kodera, Y., Maeda, T., Shimada, H., Ochiai, T., and Nomura, F. (2004). Identification of altered protein expression and post-translational modifications in primary colorectal cancer by using agarose two-dimensional gel electrophoresis. Clin Cancer Res 10, 2007-2014.



Turck, N., Richert, S., Gendry, P., Stutzmann, J., Kedinger, M., Leize, E., Simon-Assmann, P., Van Dorsselaer, A., and Launay, J. F. (2004). Proteomic analysis of nuclear proteins from proliferative and differentiated human colonic intestinal epithelial cells. Proteomics 4, 93-105.

Valenzuela, S. M., Martin, D. K., Por, S. B., Robbins, J. M., Warton, K., Bootcov, M. R., Schofield, P. R., Campbell, T. J., and Breit, S. N. (1997). Molecular cloning and expression of a chloride ion channel of cell nuclei. J Biol Chem 272, 12575-12582.

Wasch, R., and Engelbert, D. (2005). Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells. Oncogene 24, 1-10.

Wood, Z. A., Schroder, E., Robin Harris, J., and Poole, L. B. (2003). Structure, mechanism and regulation of peroxiredoxins. Trends Biochem Sci 28, 32-40.

Xin, H., Kikuchi, T., Andarini, S., Ohkouchi, S., Suzuki, T., Nukiwa, T., Hagiwara, K., Honjo, T., and Saijo, Y. (2005). Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells. Eur J Immunol 35, 1371-1380.

Yavelow, J., Tuccillo, A., Kadner, S. S., Katz, J., and Finlay, T. H. (1997). Alpha 1-antitrypsin blocks the release of transforming growth factor-alpha from MCF-7 human breast cancer cells. J Clin Endocrinol Metab 82, 745-752.
Yeh,Y.C(2003).The proteomics research of colon cancer. National Taiwan university institute of biochemical sciences master thesis.p6-7;p78-79
Yin, Z., Ivanov, V. N., Habelhah, H., Tew, K., and Ronai, Z. (2000). Glutathione S-transferase p elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases. Cancer Res 60, 4053-4057.

Yoo, B. C., Jeon, E., Hong, S. H., Shin, Y. K., Chang, H. J., and Park, J. G. (2004). Metabotropic glutamate receptor 4-mediated 5-Fluorouracil resistance in a human colon cancer cell line. Clin Cancer Res 10, 4176-4184.

Zelvyte, I., Wallmark, A., Piitulainen, E., Westin, U., and Janciauskiene, S. (2004). Increased plasma levels of serine proteinase inhibitors in lung cancer patients. Anticancer Res 24, 241-247.

Zhou, Y., Mehta, K. R., Choi, A. P., Scolavino, S., and Zhang, X. (2003). DNA damage-induced inhibition of securin expression is mediated by p53. J Biol Chem 278,
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