(18.210.12.229) 您好!臺灣時間:2021/03/05 12:27
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:林俊宇
研究生(外文):Chun-Yu Lin
論文名稱:類黃鹼素對前列腺癌細胞母代Du145及篩選出較有入侵性之子代Du145-III抑癌作用之探討
論文名稱(外文):The anti-tumor effect of flavonoids on Du145 parental cells and highly invasive potential Du145-III.
指導教授:李明亭
指導教授(外文):Ming-Ting Li
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:75
中文關鍵詞:類黃鹼素前列腺癌轉移入侵
外文關鍵詞:Du145flavonoidsMMPinvasion
相關次數:
  • 被引用被引用:0
  • 點閱點閱:106
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
類黃鹼素,主要是一群由polyphenolic物質所組成的benzo-γ-pyrone(phenylchromone)衍生物 。而類黃鹼素又可分為以下幾類:flavonols、flavans、proanthocyanidins、anthocyanidins、flavanones、flavones、isoflavones、neoflavonoids,而這些類黃鹼素廣泛的存在於水果、穀類、豆科植物、蔬菜類、堅果類、種子、草本植物、莖、花、茶、可可亞、啤酒及葡萄酒當中。根據已發表的研究指出,食用性的類黃鹼素之生物性功用包含有抗發炎、抗過敏、抗微生物、抗病毒、保護肝臟、抗凝血、心血管保護、微血管強化、抗糖尿病、抗癌以及抗癌細胞新生之作用。
本文的主要研究目的在於觀察類黃鹼素對於前列腺癌細胞的抑癌作用之探討。我們利用in vitro chemo-invasion assay的方式,成功自Du145-P母代癌細胞中篩選出分泌較多MMPs之Du145-I、Du145-II、Du145-III子代細胞。並且利用類黃鹼素Luteolin及Quercetin探討其對Du145-P及Du145-III之抑制作用。結果顯示,Luteolin及Quercetin會抑制Du145-P及Du145-III之生長,使其外型發生變化,並且誘導apoptosis的現象發生,抑制兩細胞株MMPs之釋出,抑制其轉移以及誘導web forming之能力。而EGF則與Luteolin及Quercetin有相反之效果,其能促進癌細胞之生長,促進MMPs之釋出,促進癌細胞的轉移以及web forming,同時我們比較了Du145-P與Du145-III間之差異,發現兩細胞株不僅外形上有差異,Du145-P較容易黏附在一起,而Du145-III則是較為分散,並且細胞外觀較長也較尖;而在MMPs之釋放方面,Du145-III之釋放量較Du145-P高,轉移以及web forming之能力亦高出許多。
另外我們也觀察到另一株前列腺癌細胞株PC-3,其MMPs之釋放種類亦與Du145類似,因此我們正嘗試篩選不同前列腺癌細胞PC-3、22RV1及LNCAP之第三代子代,觀察其MMPs釋放之種類,希望藉由與不同器官、組織的腫瘤細胞相比較,鑑定出特殊的organ specific MMPs,並且發展出一套可用來診斷前列腺癌的系統,也或許可提供作為新藥開發的線索。
另一方面,我們成功地篩選到能激發出紅色及綠色螢光的Du145-P及Du145-III,在未來將努力在animal model上建立一套觀察前列腺癌細胞轉移路徑的系統,以及觀察其所轉移之特異性組織與器官。另外也期望能在in vivo的系統下,實際去比較Du145-P及Du145-III之入侵能力,進一步佐證在in vitro下所得到的實驗結果。
The flavonoids, which are primary benzo-γ- pyrone ( phenylchromone) derivatives, comprise a massive group of polyphenolic compounds. The immensely diverse group broadly comprises distinct classes such as flavonols, flavans and proanthocyanidin, anthocyanidinsm flavanones, flavones, isoflavones and neoflavonoids. They are universally present in fruits, cereals, legumes, vegetables, nuts, seeds, herbs, spices, stems, flowers as well as in beverages such as tea, cocoa, beer and wine. As components of edible plants and plant foodstuffs they constiturte an integral part of the human diet. The documented biological effects of dietary flavonoids include anti-flammatory, antiallergic antimicrobial, hepatoprotective, antiviral, antithrombotic, cardioprotective, capillary strengthening, antidiabetic, anticarcinogenic and antineoplastic effects, among others.
In this thesis, we established the relatively higher invasive potential tumor cell line: Du145-I, II and III from Du145-P (parental) using Boyden chamber invasion assay. The Du145-III secreted higher amount of MMPs, higher migration and angiogenic ability as compared to Du145-P. According to the amount of MMPs secretion, migration and angiogenic ability, we concluded that Du145-III had relative higher invasive potential than that of Du145-P. Luteolin and Quercetin were documented as protein kinase inhibitor, they inhibit the activity of protein kinase by blocking the ATP binding site in catalytic unit. In this study, I tested the anti-tumor effect of Luteolin and Quercetin on Du145-P and Du145-III cells. Luteolin and Quercetin efficiently inhibit the growth of Du145-P and Du145-III cells. In addition, Luteolin and Quercetin both exert the inhibitory effect of MMPs secretion, migration and angiogenesis of Du145-P and Du145-III cells.
In a separate study, using PC-3 prostate tumor cell line, we observed that the profile of MMPs secretion is similar to that of Du145. Therefore, we intend to investigate the profile of other prostate tumor cell lines, including 22RV1 and LNCAP, in order to confirm those MMPs are organ specific.
We also established the prostate tumor cell lines Du145-P and Du145-III that could excite the red and green fluorescence. In the future, we intend to establish the animal model to observe the metastasis pathway of prostate tumor cell line by using the Du145-P and Du145-III that could excite the red and green fluorescence.
Abstract 1
中文摘要 2
第一章、前言 4
一、酪胺酸磷酸化(tyrosine phosphorylation)與癌症的關係 4
二、酪胺酸激酶(protein tyrosine kinase)及酪胺酸去磷酸酶(protein tyrosine phosphatase)之簡介 5
三、表皮生長因子受體(Epidermal growth factor receptor,EGFR)之簡介 6
四、Focal adhesion kinase(FAK)之簡介 8
五、Matrix metalloproteinases(MMPs)之簡介 9
六、類黃鹼素(Flavonoids)之簡介 10
第二章、材料與方法 13
材料: 13
方法: 13
一、細胞培養(Cell culture) 13
二、細胞之解凍與冷藏 14
三、較具侵入性(invasion potential)癌細胞之篩選 14
四、細胞生長曲線(Cell growth curve experiment) 15
五、結晶紫染色法(Crystal violet stainig) 15
六、細胞蛋白質萃取(Preparation of cell lysate) 15
七、蛋白質濃度測定(Determination of protein concentration) 16
八、SDS聚丙醯胺凝膠電泳分析(SDS polyacrylamine gel electrophoresis,SDS-PAGE) 16
九、西方墨點法分析(Western blotting) 17
十、流式細胞儀分析(Flow cytometry) 18
十一、DNA片段分析(Analysis of DNA fragmentation) 18
十二、梯度電泳分析(Gradient gel electrophoresis) 19
十三、Gelatin zymography 19
十四、Wound healing assay 20
十五、In vitro capillary formation assay 21
第三章、結果 22
壹、Du145-P與Du145-III之比較 22
一、Du145-P及Du145-III生長速率之比較 22
二、Du145-III所釋放之MMPs明顯高於Du145-P 23
三、Du145-III之轉移能力(migration ability)明顯優於Du145-P 23
四、Du145-III之web forming能力優於Du145-P 23
貳、類黃鹼素Luteolin及Quercetin對Du145-P及Du145-III之影響 24
一、Luteolin及Quercetin改變Du145-P及Du145-III之外形 24
二、Luteolin及Quercetin抑制Du145-P及Du145-III之生長 25
三、Luteolin及Quercetin具有誘導Du145-P及Du145-III癌細胞產生程式凋亡(apoptosis)之趨勢 25
四、Luteolin及Quercetin抑制Du145-P及Du145-III之MMP9的釋放,EGF則促進MMP9之釋放 26
五、Luteolin及Quercetin抑制Du145-P及Du145-III之migration,而EGF則促進其migration 26
六、Luteolin及Quercetin抑制Du145-P及Du145-III之web forming能力,而EGF則促進web forming 27
第四章、討論 48
第五章、結論 55
參考文獻 56

圖表目錄
圖一、In vitro chemo-invasion assay…………………………………………………28
圖二、Du145-P與Du145-III間型態上之差異………………………………………29
圖三、Du145-P及Du145-III生長曲線之比較………………………………………30
圖四、Du145-P與Du145-III前列腺癌細胞在EGF處理後MMPs釋放之多寡與差異之比較……………………………………………………………………..31
圖五、利用Wound-healing assay之方式檢測Du145-P與Du145-III之轉移(migration)能力……………………………………………………………32
圖六、由in vitro capillary assay觀察Du145-P與Du145-III之web forming能力……………………………………………………………………………..33
圖七、Luteolin與Quercetin對Du145-P及Du145-P型態上之影響………………..35
圖八、Luteolinu及Qucertin對Du145-P及Du145-III癌細胞生長之影響…………37
圖九、以流式細胞儀(Flow cytometry)觀察Luteolin及Quercetin對Du145-P與Du145-III癌細胞之影響…………………………………………………….39
圖十、EGF、Luteolin及Quercetin對Du145-P及Du145-III癌細胞之DNA完整性(DNA integrity)之影響…………………………………………………...40
圖十一、Luteolin、Quercetin及EGF對Du145-P及Du145-III分泌釋出MMPs之影響…………………………………………………………………………..41
圖十二、Luteolin及Quercetin及EGF對Du145-P及Du145-III癌細胞之轉移(migration)之影響…………………………………………………………46
圖十三、Luteolin、Quercetin及EGF對Du145-P及Du145-III之web forming能力之影響……………………………………………………………………..47

附錄一、Protein tyrosine phosphatase是protein tyrosine kinase之負調控因子……66
附錄二、EGF Receptor 之結構圖…………………………………………………...67
附錄三、Organization of the domains of focal adhesion kinase……………………...68
附錄四、Proposed interactions among the proteins involved in integrin signaling…..69
附錄五、Structure of human matrix metalloproteinases……………………………...70
附錄六、人類細胞中MMPs之特異性受質、染色體位置及結構組成.........................71
附錄七、the matrix metalloproteinase family…………………………......................73
附錄八、MMPs之蛋白質結構………………………………………………………74
附錄九、Functions of MMPs in cancer progression…………………………………75
Akiyama, T., Ishida, J., Nakagawa, S., Ogawara, H., Watanabe, S., Itoh, N., Shibuya, M., and Fukami, Y.(1987)Genistein, a specific inhibitor of tyrosine kinases. J Biol Chem. 262: 5592-5595.
Al-Obeidi, F.A., Wu, J.J., and Lam, K.S.(1998)Protein tyrosine kinase: structure, substrate specificity and drug discovery. Biopolymers. 47: 197-223.
Abbi, S. and Guan, J.L.(2002)Focal adhesion kinase: protein interactions and cellular functions. Histol. Histopathol. 17: 1163–1171.
Anderson, D. et al.(1990)Binding of SH2 domains of phospholipase Cγ1, GAP, and Src to activated growth factor receptors. Science 250: 979-982.
Armstrong, D.K., Isaccs, J.T., Ottavino, Y.L., and Daridson, N.E.(1992)Programmed cell death in an estrogen-independent human cancer cell line, MDA-MB-468. Cancer Res. 52:3418-3424.
Arne, Ö., and Frank, D.B.(2001)Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatases. TRENDS in Cell Bilology. 11:258-266.
Boonstra, J. et al.(1995)The epidermal growth factor. Cell. Biol. Int. 19:413-430.
Bradford, M.M.(1970)A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the protein-dye binding. Anal. Biochem. 72:248-254.
Bucci, B., D’Agnano, I., Botti, C., Mottolese, M., Carico, E., Zupi, G., and Vecchione, A.(1997)EGF-R expression in ductal breast cancer: proliferation and prognostic implications. Anticancer Res. 17:769-774.
Burke, T.R.(1992) Protein-tyrosine kinase inhibitors. Drugs of the Future. 17: 119-131.
Calalb, M. B., Polte, T. R. and Hanks, S. K. (1995). Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src family kinases. Mol. Cell. Biol. 15: 954 -963.
Carter, C.A., and Bellido, T.(1999)Decrease in protein tyrosine phosphorylation is associated with F-actin reorganization by retinoic acid in human endometrial adenocarcinoma(RL95-2)cells. J Cell Physiol. 178:320-332.
Castillo, M.H., Perkins,E., Campbell, J.H., Doerr, R., Hasset, J.M., Kandaswami, C., and Middleton, E.Jr.(1989)The effects of the bioflavonoids quercetin on squamous cell carcinoma of head and neck origin. Amer J Surgery 158: 351-355.
Ceccarelli, C., Santini, D., Chieco, P., Taffurelli, M., Marrano, D., and Mancini, A.M.(1995)Multiple expression patterns of biopathological markers in primary invasive breast carcinoma: a useful tool for elucidating its biological behavior. Ann Oncol. 6:275-282.
Chakraborti, S., Mandal, M., Das, M., Mandal, A., and Chakraborti, T.(2003)Regulation of matrix metalloproteinases: An overview. Mol. Cel. Biochem. 253: 269-285.
Cobb, B. S., Schaller, M. D., Leu, T. H. and Parsons, J. T. (1994). Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK. Mol. Cell. Biol. 14: 147 -155.
Constantinou, A., Kiguchi, K., and Huberman, E.(1990)Induction of differentiation and DNA strand breakage in human HL-60 and K-562 leukemia cells by genistein. Cancer Res. 50:2618-2624.
Crozier, A., Burns, J., Aziz, A.A., Stewert, A.J., Rabiasz, H.S., Jenkins, G.I., Edwards, C.A., Lean, M.E.(2000)Antioxidant Flavonols from fruits, vegetables and beverages. Measurements and bioavailabilty Biol. Resl. 33(2): 79-88.
Eckhart, W., Hutchinson, M.A., and Hunter, T.(1997)An activity phosphorylating tyrosine in polyoma T antigen immunoprecipitates. Cell. 18:925-933.
Edwards, J.M., Raffauf, R.F., and Quesne, W.L.(1979)Antineoplastic activity and cytotoxicity of flavones, isoflavones and flavanones. J Nat Prod. 42: 85-91.
Egeblad M. and Werb Z.(2002)New functions for the matrix metalloproteinase in cancer progression. Nat. Rev. 2: 161-174.
Far, D.F., Payron, J.F., Imbert, V., and Rossi, B.(1994)Immunofluorescent quantificantion of tyrosine phosphorylation of cellular proteins in whole cells by flow cytometry. Cytometry. 15:327-334
Fedi, P., Tronick, S.R., and Aaronson, S.A.(1997)Growth factors. In Cancer Medicine, J.F. Holland, R.C. Bast, D.L. Morton, E. Fedi, D.W. Kufe, and R.R. Weicheselbaum, eds(Baltimore, MD: Williams and Wilkins), pp. 41-64.
Fox, G. L., Rebay, I. and Hynes, R. O. (1999). Expression of DFak56, a Drosophila homolog of vertebrate focal adhesion kinase, supports a role in cell migration in vivo. Proc. Natl. Acad. Sci. USA 96: 14978 -14983.
Gabarra-Niecko, V., Schaller, M.D., and Dunty, J.M.(2003)FAK regulates biological processes important for the pathogenesis of cancer. Cancer Metastasis Rev. 22: 359–374.
Girault, J. A., Labesse, G., Mornon, J. P. and Callebaut, I. (1999). The N-termini of FAK and JAKs contain divergent band 4.1 domains. Trends Biochem. Sci. 24: 54-57.
Grandis, J.R., Melhem, M.F., Barned, E.L., and Tweardy, D.J.(1996)Quantitative immuno- histochemical analysis of transforming growth factor-alpha and epidermal growth factor receptor in patients with squamous cell carcinoma of the head and neck. Cancer. 78:1284-1292.
Griffths, K., Denis, L., Turkes, A., and Morton, M.S.(1998)Phytoestrogens and diseases of the prostate gland. Baillieres Clin Endocrinol Metab. 12: 625-647. Griffths K, Denis L, Turkes A and Morton MS: Phytoestrogens and diseases of the prostate gland. Baillieres Clin Endocrinol Metab 12: 625-647, 1998.
Gross, J. and Lapiere, C.M. (1962) Collagenolyticactivity in amphibian tissues: a tissue culture assay. Proc. Natl. Acad. Sci. U. S. A. 48: 1014–1022.
Hanahan, D.and Weinberg, R.A.(2000) The hallmarks of cancer. 100: 57-70.
Hanks, S. K., Calalb, M. B., Harper, M. C. and Patel, S. K. (1992). Focal adhesion protein-tyrosine kinase phosphorylated in response to cell attachment to fibronectin. Proc. Natl. Acad. Sci. USA 89: 8487 -8491.
Harborne, J.B.(1986)Nature, distribution, and function of plant flavonoids, in Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological, and Structure-Activity Relationships (Cody V, Middleton E, Jr and Harborne JB eds), 15-24, Alan R. Liss, Inc., New York.
Harborne, J.B. and Williams, C.A.(2000)Advances in flavonoid research since 1992. Phytochemistry 55: 481-504.
Hauck, C. R., Sieg, D. J., Hsia, D. A., Loftus, J. C., Gaarde, W. A., Monia, B. P. and Schlaepfer, D. D. (2001). Inhibition of focal adhesion kinase expression or activity disrupts epidermal growth factor-stimulated signaling promoting the migration of invasive human carcinoma cells. Cancer Res. 61: 7079 -7090.
Hecker, T.P. and Gladson, C.L.(2003)Focal adhesion kinase in cancer. Front Biosci. 8: s705–s714.
Henry, C. A., Crawford, B. D., Yan, Y. L., Postlethwait, J., Cooper, M. S. and Hille, M. B. (2001). Roles for zebrafish focal adhesion kinase in notochord and somite morphogenesis. Dev. Biol. 240: 474 -487.
Herrmann, K.(1976)Flavonols and flavones in food plants: A review. J Food Technol. 11: 433-448.
Herron, G.S., Banda, M.J., Clark, E.J., Gavrilovic, J., and Werb, Z.(1986)Secretion of metalloproteases by stimulated capillary endothelial cells. II. Expression of collagenase and stromelysin activities is regulated by endogenous inhibitors. J. Biol. Chem. 261:2814-2818.
Heussen, C., and Dowdle, E.B.(1980)Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrate. Anal. Biochem. 102:196-202.
Hildebrand, J. D., Schaller, M. D. and Parsons, J. T. (1993). Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. J. Cell Biol. 123: 993 -1005.
Hu, P. et al.(1992)Interaction of phosphatidylinositol-3-kinase-associated p85 with epidermal growth factor and platelet-derived growth factor receptors. Mol. Cell. Biol. 12: 981-990.
Hua, J., Muschel, R.(1996) Inhibition of matrix metalloproteinase nine expression by a ribozyme blocks metastasis in a rat sarcoma model system. Cancer Res 56:5279–5284.
Huang, Y.T., Hwang, J.J., Lee, P.P., Ke, F.C., Huang, J.H., Huang, C.J., Kandaswami, C., Middleton, E.Jr. and Lee, M.T.(1999)Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacology. 128: 999-1010.
Hubbard, S.R. and Till, J.H.(2000)Protein tyrosine kinase structure and function. Annu. Rev. Biochem. 69:373–398.
Hunter, T.(1989)Protein-tyrosine phosphatases: the other side of the coin. Cell. 58(6): 1013-1016.
Hunter, T.(1995)Protein kinase and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 80:225-236.
Hunter, T.(1998)The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role in cell growth and disease. Philos Trans R Soc Lond B Biol Sci. 353:583-605.
Jost, M., Kari, C., and Rodeck, U.(2000)The EGF receptor- an essential regulator of multiple epidermal functions. Eur J Dermatol. 10:505-510.
Ka¨ha¨ri, V.-M., and Saarialho-Kere, U. (1997) Matrix metalloproteinases in skin. Exp. Dermatol. 6: 199–213.
Kandaswami, C., Perkins, E., Soloniuk, D.S., Drzewiecki, G., and Middleton, E.Jr.(1991)Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro. Cancer Lett. 56: 147-152.
Kandaswami, C., and Middleton, E.Jr.(1994)Free radical scavenging and antioxidant activity of plant flavonoids. Advance in Experimental Medicine & Biology 366: 351-376
Kandaswami, C., and Middleton, E.Jr.(1997)Flavonoids as antioxidants. In: Natural Antioxidants. Ed. Shahihi E, ACS Press, Champagne, Illinois. 174-203.
Kappagoda, C.T., Karim, M., McCormic, K., and Kandaswami, C.(2000)Unraveling the French paradox. Chem. Innov. 30(9): 26-31.
Kefford, J.F., and Chandler, B.V.(eds)(1970)The Chemical Constituents of Citrus Fruits. Academic Press, New York.
Kelloff, G.J., Fay, J.R., Steele, V.E., Lubet, R.A., Boone, C.W., Crowell, J.A., and Sigman, C.C.(1996)Epidermal growth factor receptor tyrosine kinase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev. 5:657-666.
Klijn, J.G., Berns, P.M., Schmitz, P.I., and Foekens, J.A.(1992)The clinical significance of epidermal growth factor receptor(EGF-R)in human breast cancer: a review on 5232 patients. Endocr Rev. 13:3-17.
Kolibaba, K.S., and Drucker, B.J.(1997)Protein kinase and inhibitor. Biochim et Biophy Acta. 1333: F217-F248.
Kühnau, J.(1976)The flavonoids: A class of semi-essential food components: Their role in human nutrition. World Rev Nutr Diet. 24: 117-191.
Kyle, E., Neckers, L., Takimoto, C., Curt, G., and Bergan, R.(1997)Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. Mol Pharmacol. 51: 193-200.
Laemmli, U.K.(1970)Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227:680-685.
Lee, L.T., Huang, Y.T., Hwang, J.J., Lee, H.P.P., Ke, F.C., Nair, M.P., Kandaswain, C., and Lee, M.T.(2002) Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res. 22: 1615-1628.
Lee, L.T., Huang, Y.T., Hwang, J.J., Amy, Y.L.L., Ke, F.C., Huang, C.J., Kandaswami, C., Lee, H.P.P., and Lee, M.T.(2004)Transinactivation of the epidermal growth factor receptor tyrosine kinase and focal adhesion kinase phosphorylation by dietary flavonoids: effect on invasive potential of human carcinoma cells. Biochem. Pharmacol. 67:2103-2114.
Levitzki, A., and Gazit, A.(1995)Tyrosine kinase inhibition: an approach to drug development. Science. 267:1782-1788.
Liabakk, N.B., Talbot, I., Smith, R.A., Wilkinson, K., Balkwill, F.R.(1996)Matrix metalloproteinases 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res. 56:190–196.
Lin S.Y., Makino K., Xia W., Matin A., Wen Y., Kwong K.Y., Bourguignon L., and Hung M.C.(2001)Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat. Cell. Biol. 3: 802-808.
Lower, E.E., Miller, M.A., Williams, L., Westermann, C., and Heffelfinger, S.(1995)Increased phosphotyrosine in breast cancer tissue is associated with a worse prognosis. Breasr Cancer Res Treat. 35:277-282.
Majercakova, P.(2000)Role of protein phosphorylation in the development of tumors. Sb Lek. 101:215-228.
Martin, K. H., Boerner, S. A. and Parsons, J. T. (2002). Regulation of focal adhesion targeting and inhibitory functions of the FAK related protein FRNK using a novel estrogen receptor "switch". Cell Motil. Cytoskeleton 51: 76-88.
McDonnell, T.J., and Korsmeyer, S.J.(1991)Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 349:254-256.
McLean, G.W., Avizienyte, E., and Frame, M.C.(2003)Focal adhesion kinase as a potential target in oncology. Expert Opin. Pharmacother. 4: 227–234.
Middleton, E.Jr., and Kandaswami, C.(1992)Effects of flavonoids on immune and inflammatory cell function. Biochem. Pharmaco. 43: 1167-1179.
Middleton, E.Jr., and Kandaswami, C.(1993)The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer. In: “The Flavonoids: Advances in Research” (eds. Harborne JB), Chapman and Hall, London. 619-649.
Middleton, E.Jr., and Kandaswami, C.(1994)Potential health-promoting properties of citrus flavonoids. Food Technology 48: 115-119.
Middleton, E.Jr., Kandaswami, C., and Theoharidis, T.C.(2000)The impact of plant flavonoids on mammalian biology: implications for inflammations, heart disease and cancer. Pharmacological Review 52: 673-751.
Molnar, J., Beladi, I., Domonkos, K., Foldeak, S., Boda, K., and Veckenstedt, A.(1981)Antitumor activity of flavonoids on NK/Ly ascites tumor cells. Neoplasma. 28: 11-18.
Moghal, N., and Sternberg, P.W.(1999)Multiple positive and negative regulators of signaling by the EGF-receptor. Curr Opin Cell Biol. 11:190-196.
Nagai, Y. et al. (1966) Tadpole collagenase. Preparation and purification. Biochemistry 5: 3123–3130.
Naylor, M.S., Stamp, G.W., Davies, B.D., Balkwill, F.R.(1994)Expression and activity of MMPs and their regulators in ovarian cancer. Int J Cancer 58:50–56.
Neet, K., and Hunter., T.(1996)Vertebrate non-receptor protein-tyrosine kinase families. Genes Cell. 1:147-169.
Nguyen, L., Chapdelaine, A., and Chevalier, S.(1990)Prostatic acid phosphatase in serum of patients with prostatic cancer is a specific phosphotyrosine acis phosphatase. Clin Chem. 36:1450-1455.
Palmer, R. H., Fessler, L. I., Edeen, P. T., Madigan, S. J., McKeown, M. and Hunter, T. (1999). DFak56 is a novel Drosophila melanogaster focal adhesion kinase. J. Biol. Chem. 274: 35621 -35629.
Parsons, J.T.(2003)Focal adhesion kinase: the first ten years. J. Cell. Sci. 116: 1409-1416.
Pierpoint, W.S.(1986)Flavonoids in the human diet, in Plant Flavonoids in Biology and Medicine: Biochemical, Pharmacological, and Structure-Activity Relationships (Cody, V., Middleton, E., and Harborne, J.B. eds) 125-140, Alan R. Liss, Inc., New York.
Powis, G.(1994)Signaling pathways as targets for anticancer drug development. Pharmacol Ther. 62: 57-95.
Richardson, A., Malik, R. K., Hildebrand, J. D. and Parsons, J. T. (1997). Inhibition of cell spreading by expression of the C-terminal domain of focal adhesion kinase (FAK) is rescued by coexpression of Src or catalytically inactive FAK: a role for paxillin tyrosine phosphorylation. Mol. Cell. Biol. 17: 6906 -6914.
Riese, D.J. 2nd, and Stern, D.F.(1998)Specificity within the EGF family/ErbB receptor family signaling network. Bioessays. 20:41-48.
Rijksen, G., Adriaansen-Slot, S.S., and Staal, G.E.(1996)An enzyme-linkd immunosorbent assay for the determination of src-family tyrosine kinase activity in breast cancer. Breast Cancer Res Treat. 39:139-145.
Salomon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A., and McGuire, W.L.(1987)Human breast cancer: correlation of relapse and survival with amplification of the HER2/neu oncogene. Science. 235: 177-182.
Salmon, D.S., Brandt, R., Ciardiello, F., and Normanno, N.(1995)Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 19:183-232.
Samuels, M.A., Weber, M.J., Bishop, J.M., and Mcmahon, M.(1993). Conditional transformation of cells and rapid activation of the mitogen-activated protein linase cascade by an estradiol-dependent human raf-1 protein kinase. Mol. Cell. Biol., 13:6241-6252.
Sato, F., Matsukawa, Y., Matsumoto, K., Nishino, H., and Sakai, T.(1994)Apegenin induces morphological differentiation and G2/M arrest in rat neuronal cells. Biochem Biophys Res Comm. 204: 578-584.
Scambia, G., Ranelletti, F.O., Benedetti Panici, P., Piantelli, M., Bonanno, G., De Vincenzo, R., Ferrandina, G., Rumi, C., Larocca, L.M., and Mancuso, S.(1990) Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells. Br J Cancer. 62: 942-946.
Schlaepfer, D.D., Hauck C.R., and Sieg, D.J.(1999)Signaling through focal adhesion kinase. Prog. Biophys. Mol. Biol. 71: 435–478.
Schaller, M. D., Borgman, C. A., Cobb, B. S., Vines, R. R., Reynolds, A. B. and Parsons, J. T. (1992). pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. Proc. Natl. Acad. Sci. USA 89: 5192 -5196.
Schaller, M. D., Borgman, C. A. and Parsons, J. T. (1993). Autonomous expression of a noncatalytic domain of the focal adhesion-associated protein tyrosine kinase pp125FAK. Mol. Cell. Biol. 13: 785 -791.
Schaller, M. D., Hildebrand, J. D., Shannon, J. D., Fox, J. W., Vines, R. R. and Parsons, J. T. (1994). Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src. Mol. Cell. Biol. 14:1680 -1688.
Schaller, M. D., Otey, C. A., Hildebrand, J. D. and Parsons, J. T. (1995). Focal adhesion kinase and paxillin bind to peptides mimicking beta integrin cytoplasmic domains. J. Cell Biol. 130: 1181 -1187.
Schaller, M. D., Hildebrand, J. D. and Parsons, J. T. (1999). Complex formation with focal adhesion kinase: A mechanism to regulate activity and subcellular localization of Src kinases. Mol. Biol. Cell 10: 3489 -3505.
Schaller, M.D.(2001)Biochemical signals and biological responses elicited by the focal adhesion kinase. Biochim. Biophys. Acta. 1540: 1–21.
Schlessinger, J.(2000)Cell signaling by receptor tyrosine kinases. Cell 103: 211–225.
Schneider, M.R., Schirner, M.(1993)Antimetastatic prostacyclin analog. Drugs Future 18:29–48.
Schraag, B., Staal, G.E., Adriaansen-Slot, S.S., Salden, M., and Rijksen, G.(1993)Standardization of an enzy,e-linked immunosorbent assay for the determination of protein tyrosine kinase activity. Anal Biochem. 211:233-239.
Shay, J.W., and Bacchetti, S.(1997)A survey of telomerase activity in human cancer. Eur J Cancer. 33:787-791.
Sieg, D. J., Hauck, C. R. and Schlaepfer, D. D. (1999). Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J. Cell Sci. 112:2677 -2691.
Sieg, D. J., Hauck, C. R., Ilic, D., Klingbeil, C. K., Schaefer, E., Damsky, C. H. and Schlaepfer, D. D. (2000). FAK integrates growth-factor and integrin signals to promote cell migration. Nat. Cell Biol. 2: 249 -256.
Soulinna, E. M., Buchsbaum, R. N., and Racker, E.(1975)The effect of flavonoids on aerobic glycolysis and growth of tumor cells. Cancer Res 35: 1865-1872.
Sun, C. X., Robb, V. A., and Gutmann, D. H. (2002). Protein 4.1 tumor suppressors: getting a FERM grip on growth regulation. J. Cell Sci. 115: 3991- 4000.
Stehelin, D., Varmus, H. E., Bishop, J. M., and Vogt, P.(1970)DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature. 260: 170-173.
Sternlicht, M. D. and Werb, Z.(2001)How matrix metalloproteinases regulatecell behavior. Annu. Rev. Cell Dev. Biol. 17: 463-516.
Sweeney, C., and Carraway, K.L.(2000)Ligand discrimination by ErbB receptors: differential signaling through differential phosphorylation site usage. Oncogene. 19:5568-5573.
Taylor, J. M., Mack, C. P., Nolan, K., Regan, C. P., Owens, G. K. and Parsons, J. T. (2001). Selective expression of an endogenous inhibitor of FAK regulates proliferation and migration of vascular smooth muscle cells. Mol. Cell. Biol. 21: 1565 -1572.
Thomas, J. W., Cooley, M. A., Broome, J. M., Salgia, R., Griffin, J. D., Lombardo, C. R. and Schaller, M. D. (1999). The role of focal adhesion kinase binding in the regulation of tyrosine phosphorylation of paxillin. J. Biol. Chem. 274: 36684 -36692.
Toutant, M., Costa, A., Studler, J. M., Kadare, G., Carnaud, M. and Girault, J. A. (2002). Alternative splicing controls the mechanisms of FAK autophosphorylation. Mol. Cell. Biol. 22: 7731 -7743.
Towbin, H., Staehelin, T., and Gordon, J.(1979)Electrophoretic transfer of proteins from poly-acrylamide gels to nitrocellular sheets: procedure and some application. Proc. Natl. Acad. Sci. U.S.A. 76:4350-4354.
Van der Geer, P., Hunter, T., and Mizuno, K.(1999)Receptor protein-tyrosine kinases and their signal transduction pathways. Annu Rev Cell Biol. 10:251-337.
Watson, S.A., Morris, T.M., Robinson, G., Crimmin, M.J., Brown, P.D., Hardcastle, J.D.(1995) Inhibition of organ invasion by the metalloproteinase inhibitor Batimastat (BB-94) in two human colon carcinoma metastasis models. Cancer Res 55:3629–33.
Wei, Y.Q., Zhao, X., Kariya, Y., Fukata, H., Teshigawara, K., and Uchida, A.(1994) Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res. 54: 4952-4957.
Weinberg, R.A.(1995)The molecular basis of oncogenes and tumor suppressor genes. Ann. N. Y. Acad. Sci. 758: 331-338.
Wells, A.(1999)EGF receptor. Int J Biochem Cell Biol. 31:637-643.
Xiong, W. and Parsons, J. T. (1997). Induction of apoptosis after expression of PYK2, a tyrosine kinase structurally related to focal adhesion kinase. J. Cell Biol. 139:529 -539.
Yang, X., Jia, X., Corvalan, J.R., Wang, P., and Davis, C.G.(2001)Development of ABX-EGF, a fuuly human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 38:17-23.
Yarden, Y., and Ullrich A.(1987)EGF and erbB2 receptor over-expression in human tumors. Growth factor receptor tyrosine kinases. Annu. Rev. Biochem. 57, 443-478.
Zhang, L., Lau, Y.K., Xi, L., Hong, R.L.,Kim, D.S.H.L., Chang, C.J. (1998)Tyrosine kinase inhibitors, emodin and its derivative repress Her-2/neu–induced cellular transformation and metastasis-associated properties. Oncogene 16:. 2855–2863.
Zwick, E., Hackel, P.O., Prenzel, N., and Ullrich, A.(1999)The EGF receptor as central transducer of heterologous signaling systems. Trends Pharmacol Sci. 20:408-412.
Watson, S.A., Morris, T.M., Robinson, G., Crimmin, M.J., Brown, P.D., Hardcastle, J.D.(1995)Inhibition of organ invasion by the metalloproteinase inhibitor Batimastat (BB-94) in two human colon carcinoma metastasis models. Cancer Res 55:3629–33.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔