Responsive image
博碩士論文 etd-0808100-123811 詳細資訊
Title page for etd-0808100-123811
論文名稱
Title
第一部份:國人鼻咽癌檢體中p16,p27和Rb腫瘤抑制基因表現之分析 第二部分:新建立鼻咽癌細胞株之腫瘤特性分析
Part I:Analysis of the tumor suppressor gene p16,p27 and Rb expression in nasopharyngeal carcinoma in Taiwan Part II:Tumor characteristics of two newly established nasopharyngeal carcinoma cell lines
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
103
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
2000-06-29
繳交日期
Date of Submission
2000-08-08
關鍵字
Keywords
腫瘤抑制基因、鼻咽癌
nasopharyngeal carcinoma, tumor suppressor gene
統計
Statistics
本論文已被瀏覽 5664 次,被下載 5406
The thesis/dissertation has been browsed 5664 times, has been downloaded 5406 times.
中文摘要
第一部份
鼻咽癌是中國南方常發生的惡性腫瘤,多種與鼻咽癌有關的危險因子已被發現,但鼻咽癌形成的分子機制仍不是很清楚。為了要研究c-myc、cyclin D1、p16、p27及Rb蛋白在鼻咽癌中的表現情形,我們使用免疫組織染色的方法,偵測46個南台灣鼻咽癌檢體。有31/45(69﹪)的檢體沒有p16蛋白的表現;Rb蛋白34/46(73.9﹪)強烈表現;29/41(70.7﹪)有c-myc蛋白的表現;cyclin D1在鼻咽癌中沒有過量表現的情形;p27有32/46(69.6﹪)呈現較高的表現量,與其它腫瘤呈現相反的關係。除了c-myc 沒有表現的病人易發生頸部轉移(P<0.05),其它蛋白與病人的臨床疾病特性都沒有顯著的相關性。
第二部分
為了要更瞭解鼻咽癌,我們探討新建立兩株鼻咽癌細胞株(NPCGK 01, NPCGK 02)之腫瘤特性。鼻咽癌腫瘤檢體作初代培養,並建立細胞株後做腫瘤特性分析。NPCGK 01為分化癌,NPCGK 02為未分化癌。兩株細胞繼代超過25代。兩株細胞都有染色體終端酵素活性;都會表現hTERT基因;keratin-19表現量都很強;TGFâ第一型接受體表現量較多;且c-myc、c-fos及cyclin D1三種致癌基因都有過量表現的情形;Rb蛋白表現較正常上皮細胞強;分化癌細胞株的p16基因具有降調節的情形且p27基因幾乎不表現,但p21蛋白則過量表現。總之,兩株鼻咽癌細胞生長能力較正常細胞強,具有一般癌細胞生長特性,致癌蛋白都過量表現,腫瘤抑制蛋白表現不正常,這些因素可能都與鼻咽癌的發生有極大的關係。
Abstract
第一部份
Nasopharyngeal carcinoma(NPC) is a malignant tumor which occurs at high incidence in southern China. Several risk factors have now been recognized, but the molecular mechanism of this disease is not well understood. To investigate the c-myc、cyclin D1、p16、p27 and Rb gene expression in NPC at protein level, 46 cases of nasopharyngeal carcinoma in southern Taiwan were detected by immunohistochemistry. There was no detectable p16 in 31/45 cases(69﹪); 34/46 cases(73.9﹪)had intense staining for the Rb protein; 29(70.7﹪)of 41 cases had c-myc protein expression;cyclin D1 was not overexpression in nasopharyngeal carcinoma; 32(69.6﹪)of 46 cases had high level expression of p27, which was inverse correlation with other tumors. No expression of c-myc protein correlated with higher neck metastasis(P<0.05). No correlation was found between other proteins and any of the clinicopathological parameters.

第二部份
To better understand nasopharyngeal carcinoma(NPC), we have newly established two NPC cell lines. Biopsy specimens from NPC patients were collected, primary culture were set up. Two NPC cell lines were established:NPCGK 01 was derived from differentiated carcinoma and NPCGK 02 was derived from undifferentiated carcinoma. Two cell lines have been passaged for more than 25 times. Two cell lines had telomerase activity;strong expression of hTERT gene and keratin-19 gene were also observed. TGFβ RI protein expression of these NPC cell lines is higher than normal epithelial cell.The oncogenes, c-myc、c-fos and cyclin D1 were overexpressed. The Rb protein was expressed stronger than normal epithelial cells. NPCGK 01 that was derived from differentiated carcinoma had p16 down-regulation and p27 gene not expression, but p21 protein had excess expression. In short, two cell lines had cancer cell characteristics, oncoproteins were overexpression and tumor suppressor proteins were abnormal expression. This result may lead to tumorigenesis of nasopharyngeal carcinoma.
目次 Table of Contents
第一部份:
壹、緒論-------------------------------------- -1
一、前言----------------------------------------1
二、細胞週期------------------------------------2
三、各論----------------------------------------3
(一)致癌基因------------------------------- --4
(二)腫瘤抑制基因-----------------------------10
四、總結---------------------------------------16
五、鼻咽癌-------------------------------------18
貳、研究目的-----------------------------------24
參、材料與方法---------------------------------25
一、材料-------------------------------------- 25
二、方法
 免疫組織化學染色法---------------------------25
三、統計分析方法-------------------------------26
肆、實驗結果-----------------------------------27
伍、討論---------------------------------------43
圖:
圖1.------------------------------------------5
圖2.-----------------------------------------19
圖3.-----------------------------------------30
圖4.-----------------------------------------35
圖5.-----------------------------------------38
圖6.-----------------------------------------39
圖7.-----------------------------------------40
圖8.-----------------------------------------41
圖9.-----------------------------------------42

表:
表1.-----------------------------------------19
表2.-----------------------------------------30
表3.-----------------------------------------32
表4.-----------------------------------------43

第二部分:
壹、緒論---------------------------------------47
貳、研究目的-----------------------------------60
參、材料與方法
一、鼻咽癌細胞初代培養-------------------------61
二、固著非依賴性生長分析-----------------------62
三、Total RNA之萃取----------------------------63
四、反轉錄聚合酵素連鎖反應---------------------63
五、西方墨點分析-------------------------------64
1. 蛋白質的萃取--------------------------------64
2. 蛋白質定量----------------------------------64
3. SDS-聚丙烯醯銨膠體電泳的製作--------------- 65
4. 電泳及轉漬----------------------------------66
5. blocking----------------------------------- 67
6. 初級抗體作用--------------------------------67
7. 次級抗體作用--------------------------------68
8. 檢測蛋白質----------------------------------68
六、終端酵素活性之偵測-------------------------69
七、Cytokeratin-19定量分析---------------------70
八、免疫細胞染色法-----------------------------70
肆、結果---------------------------------------74
伍、討論---------------------------------------89
陸、參考文獻-----------------------------------93
圖:
圖1.-----------------------------------------43
圖2.-----------------------------------------77
圖3.-----------------------------------------79
圖4.-----------------------------------------82
圖5.-----------------------------------------85
圖6.-----------------------------------------88

表:
表1.-----------------------------------------72
表2.-----------------------------------------73
參考文獻 References
Bartkova, J., Lukas, J., Muller, H., Strauss, M., Gusterson, B., and Bartek, J. Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Res., 55: 949-956, 1995.

Bartkova, J., Lukas, J., Strauss, M., and Bartek J. Cell cycle-related variation and tissue-restricted expression of human cyclin D1 protein. J. Pathology, 172: 237-245, 1994.

Blackburn, E. H. Structure and function of telomeres. Nature, 350: 569-573, 1991.

Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., and Wright, W. E. Extension of life-span by introduction of telomerase into normal human cells. Science, 279: 349-352, 1998.

Buckley, M. F., Sweeney, K., J., Hamilton, J. A., Sini, R. L., Manning, D. L., Nicholson, R. I., deFazio, A., Watts, C. K., Musgrove, E. A., and Sutherland, R. L. Expression and amplification of cyclin genes in human breast cancer. Oncogene, 8: 2127-2133, 1993.

Bukholm, I. K., Berner, J. M., Nesland, J. M., and Børresen-Dale, A.-L. Expression of cyclin Ds in relation p53 status in human breast carcinomas. Virchows Arch., 433: 223-228, 1998.

Coppee, F., Depoortere, F., Bartek, J., Ledent, C., Parmentier, M., and Dumont, J. E. Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumors. Oncogene, 17: 631-641, 1998.

Counter, C. M., Avilion, A. A., Lefeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., and Bacchetti, S. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J., 11: 1921-1929, 1992.

Counter, C. M., Hang, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., Sedivy, J. M., and Weinberg, R. A. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc. Natl. Acad. Sci. USA, 95: 14723-14728, 1998.

Counter, C. M., Meyerson, M., Eaton, E. N., Ellisen, L. W., Caddle, S. D., Haber, D. A., and Weinberg, R. A. Telomerase activity is restored in human cells by ectopic expression of hTERT(hEST2), the catalytic subunit of telomerase. Oncogene, 16:1217-1222, 1998.

de Boer, C. J., Loyson, S., Kluin, P. M., Kluin, N. H. C., Schuuring, E., and van Krieken, J. H. Multiple breakpoints within the BCL-1 locus in B-cell lymphoma: rearrangements of the cyclin D1 gene. Cancer Res., 53: 4148-4152, 1993.

Depoortere, F., Pirson, I., Bartek, J., Dumont, J. E., and Roger, P. P. Transforming growth factor β1 selectively inhibits the cyclin AMP-dependent proliferation of primary thyroid epithelial cells by preventing the association of cyclin D3-cdk4 with nuclear p27kip1. Mol. Biol. Cell, 11: 1061-1076, 2000.

Dickson, M. A., Hahn, W. C., Ino, Y., Ronfard, V., Wu, J. Y., Weinberg, R. A., Louis, D. N., Li, F. P., and Rheinwald, J. G. Human keratinocytes that express hTERT and also bypass a p16INK4a–enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol. Cell Biol., 20: 1436-1447, 2000.

Einat, M., Resnitzky, D., and Kimchi A. Close link between reduction of c-myc expression by interferon and G0/G1 arrest. Nature, 313: 597-560, 1985.

El-Naggar, A. K., Lai, S., Clayman, G. L., Zhou, J. -H., Tucker, S. A., Myers, J., Luna, M. A., and Benedict, W. F. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: Biological and clinical implications. Hum. Pathol., 30: 1013-1018, 1999.

El-Naggar, A. K., Lai, S., Clayman, G., Lee, J.-K. J., Luna, M. A., Goepfert, H., and Batsakis, J. G. Methylation, a major mechanism of p16/CDKN1 gene inactivation in head and neck squamous carcinoma. Am. J. Path., 151: 1767-1774, 1997.

Erdamar, S., Yang, G., Harper, J. W., Lu, X., Kattan, M. W., Thompson, T. C., and Wheeler, T. M. Level of expression p27kip1 of protein in human prostate and prostate cancer: An immunohistochemical analysis. Mod. Pathol., 12: 751-755, 1999.

Fan,C. S., Wong, N., Leung, S. F., To, K. F., Lo, K. W., Lee, A. W., Mok, T, S.-K., Johnson, P. J., and Huang, D. P. Frequent c-myc and int-2 overrepresentations in nasopharyngeal carcinoma. Hum. Pathol., 31: 169-178, 2000.

Feng, J., and 14 others. The RNA component of human telomerase. Science, 269: 1236-1241, 1995.

Field, J. K., Spandidos, D. A., Stell, P. M., Vaughan, E. D., Evan, G. I., and Moore, J. P. Elevated expression of the c-myc oncoprotein correlates with poor prognosis in head and neck squamous cell carcinoma. Oncogene, 4: 1463-1468, 1989.

Filmus, J., and Kerbel, R. S. Development of resistance mechanisms to the growth-inhibitory effects of transforming growth factor beta during tumor progression. Curr. Opin. Oncol., 5: 123-129, 1993.

Fredersdorf, S., Burns, J., Milne, A. M., Packham, G., Fallis, L., Gillett, C. E., Royds, J. A., Peston, D., Hall, P. A., Hanby, A. M., Barnes, D. M., Shoushe, S., O’Hare, M. J., and Lu, X. High level expression of p27kip1 and cyclin D1 in some human breast cancer cells: Inverse correlation between the expression of p27kip1 and degree of malignancy in human breast and colorectal cancer. Proc. Natl. Acad. Sci. USA, 94: 6380-6385, 1997.

Gamberi, G., Benassi, M. S., Bohling, T., Ragazzini, P., Molendini, L., Sollazzo, M. R., Pompetti, F., Merli, M., Magagnoli, G., Balladelli, A., and Picci, P. C-myc and c-fos in human osteosarcoma: prognostic value of mRNA and protein expression. Oncology, 55: 556-563, 1998.

Gansauge, S., Gansauge, F., Ramadani, M., Stobbe, H., Rau, B., Harada, N., and Beger, H. G. Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis. Cancer Res., 57: 1634-1637, 1997.

Garcia, J. F., Villuendas, R., Algara, P., Sáez, A. I., Sánchez-Verde, L., Martinez-Montero, J. C., Martinez, P., and Piris, M. A. Loss of p16 protein expression associated with methylation of the p16INK4A gene is a frequent finding in Hodgkin’s disease. Lab. Invest., 79: 1453-1459, 1999.

Geradts, J., Kratzke, R. A., Niehans, G. A., and Lincoln, C. E. Immunohistochemical Detection of the cyclin-dependent kinase inhibitor 2/ multiple tumor suppressor gene 1(CDKN1/MTS1) product p16INK4 in archival human solid tumors: correlation with retinoblastoma protein expression. Cancer Res., 55: 6006-6011, 1995.

Greenberg, R. A., O’Hagan, R. C., Deng, H., Xiao, Q., Hann, S. R., Adams, R. R., Lichtsteiner, S., Chin, L., Morin, G. B., and DePinho, R. A. Telomerase reverse transcriptase gene is a direct target of c-myc but is not functionally equivalent in cellular transformation. Oncogene, 18: 1219-1226, 1999.

Greider, C. W., and Blackburn, E. H. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature, 337: 331-337, 1989.

Gulley, M. L., Nicholls, J. M., Schneider, B. G., Amin, M. B., Ro, J. Y., and Geradts, J. Nasopharyngeal carcinomas frequently lack the p16/mts1 tumor suppressor protein but consistently express the retinoblastoma gene product. Am. J. Pathol., 152: 865-869, 1998.

Ho, S., Leung, W.T., Yuen, J., and Johnson, P. J. Serum levels of CYFRA 21-1 in nasopharyngeal carcinoma and its possible role in monitoring of therapy. Eur. J. Cancer B. Oral. Oncol., 32B: 377-380, 1996.

Jiang, W., Kahn, S. M., Tomita, N., Zhang, Y.-J., Lu, S.-H., and Weinstein, I. B. Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res., 52: 2980-2983, 1992.

Jiang, X. R., Jimenez, G., Chang, E., Frolkis, M., Kusler, B., Sage, M., Beeche, M., Bodnar, A. G., Wahl, G. M., Tlsty, T. D., and Chiu, C. P. Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Nature Genet., 21: 111-114, 1999.

Kanaya, T., Kyo, S., Takakura, M., Ito, H., Namiki, M., and Inoue, M. hTERT is a critical determinant of telomerase activity in renal-cell carcinoma. Int. J. Cancer, 78: 539-543, 1998.

Kang, S. H., Bang, Y. J., Jong, H. S., Seo, J. Y., Kim, N. K., and Kim, S. J. rapid induction of p21WAF1 but delayed down-regulation of Cdc25A in the TGF-β-induced cell cycle arrest of gastric carcinoma cells. British J. Cancer, 80: 1144-1149, 1999.

Kelly, D. L., and Rizzino, A. Growth regulatory factors and carcinogenesis: the roles played by transforming growth factor beta, its receptors and signaling pathways. Anticancer Res., 19: 4791-4807, 1999.

Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L., Coviello, G. M., Wright, W. E., Weinrich, S. L., and Shay, J. W. Specific association of human telomerase activity with immortal cells and cancer. Science, 266: 2011-2015, 1994.

Kiyono, T., Foster, S. A., Koop, J. I., McDougall, J. K., Galloway, D. A., and Klingelhutz, A. J. Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells. Nature, 396: 84-88, 1998.

Knudson, A. G. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA, 68: 820-823, 1971.

Kyo, S., Takakura, M., Taira, T., Kanaya, T., Itoh, H., Yutsudo, M., Ariga, H., and Inoue, M. Sp1 cooperates with c-myc to activate transcription of the human telomerase reverse transcriptase gene(hTERT). Nucleic Acids Res., 28: 669-677, 2000.

Kyo, S., Ueno, H., Kanaya, T., and Inoue, M. Telomerase activity in gynecological tumors. Clin. Cancer Res., 2: 2023-2028, 1996.

Latil, A., Vidaud, D., Valéri, A., Fournier, G., Vidaud, M., Lidereau, R., Cussenot, O., and Bièche, I. hTERT expression correlates with myc over-expression in human prostate cancer. Int. J. Cancer, 89: 172-176, 2000.

Lee, W. H., Bookstein, R., Hong, F., Young, L. J., Shew, J. Y., and Lee, E. Y. Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science, 235: 1394-1399, 1987.

Lee, H. Y., Chaudhary, J., Walsh, G. L., Hong, W. K., and Kurie, J. M. Suppression of c-fos gene transcription with malignant transformation of human bronchial epithelial cells. Oncogene, 16: 3039-3046, 1998.

Lin, G.T., Chan, W. Y., Chen, W., and Shew, J. Y. Nasopharyngeal carcinoma and retinoblastoma gene expression. Lab. Invest., 67: 56-70, 1992.

Lin, Y., Miyamoto, H., Fujinami, K., Umemura, H., Hosaka, M., Iwasaki, Y., and Kubota, Y. Telomerase activity in human bladder cancer. Cancer Res., 2: 929-932, 1996.

Lin, J. C., Tsai, C. S., Wang, W. Y., and Jan, J. S. Detection of circulating tumor cells in venous blood of nasopharyngeal carcinoma patients by nested reverse transcriptase-polymerase chain reaction. Kao Hsiung I Hsueh. Tsa. Chih., 16: 1-8, 2000.

Lo, K. W., Cheung, S. T., Leung, S. F., van Hasselt, A., Tsang, Y. S., Mak, K. F., Chung, Y. F., Wook, J. K., Lee, J. C., and Huang, D. P. Hypermethylation of the p16 gene in nasopharyngeal carcinoma. Cancer Res., 56:2721-2725, 1996.

Luo, J., Xiao, J., Tao, Z., and Li, X. Detection of c-myc gene expression in nasopharyngeal carcinoma by nonradioactive in situ hybridization and immunohistochemistry. Chin. Med. J., 110: 229-232, 1997.

Malandsmo, G. M., Flørenes, V. A., Hovig, E., Øyjord, T., Engebraaten, O., Holm, R., Børresen, A.-L., and Fodstad, Ø. Involvement of the pRb/p16/cdk4/cyclin D1 pathway in the tumorigenesis of sporadic malignant melanomas. Br. J. Cancer, 73: 909-916, 1996.

Markowitz, S. D., and Roberts, A. B. Tumor suppressor activity of the TGF-beta pathway in human cancers. Cytokine Growth Factor Rev., 7: 93-102, 1996.

Massagué, J. TGFβ signal transduction. Annu. Rev. Biochem., 67: 753-791, 1998.

Matsushime, H., Quell, D. E., Shurtleff, S. A., Shibuya, M., Sherr, C. J., and Kato, J.-Y. D-type cyclin-dependent kinase activity in mammalian cells. Mol. Cell. Biol., 14: 2066-2076, 1994.

McGarvey, T. W., Tait, E., Tomaszewski, J. E., and Malkowicz, S. B. Expression of transforming growth factor-beta receptors and related cell-cycle components in transitional-cell carcinoma of the bladder. Mol. Urol., 3: 371-380, 1999.

Merlo, A., Herman, J. G., Mao, L., Lee, D. J., Gabrielson, E., Burger, P. C., Baylin, S. B., and Sidransky, D. 5’ CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/cdkn2/mts 1 in human cancer. Nat. Med., 1: 686-692, 1995.

Mineta, H., Miura, K., Suzuki, I., Takebayashi, S., Misawa, K., Ueda, Y., and Ichimura, K. p27 expression correlates with prognosis in patients with hypopharyngeal cancer. Anticancer Res., 19: 4407-4412, 1999.

Miyazaki, M., Ohashi, R., Tsuji, T., Mihara, K., Gohda, E., and Namba, M. Transforming growth factor-β1 stimulates or inhibits cell growth via down- or up- regulation of p21/Waf1. Biochem. Biophys. Res. Commun., 246: 873-880, 1998.

Morales, C. P., Holt, S. E., Ouellette, M., Kaur, K. J., Yan, Y., Wilsonm K. S., White, M. A., Wright, W. E., and Shay, J. W. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nature Genet., 21: 115-118, 1999.

Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M., Deaven, L L., Jones, M. D., Meyne, J., Ratliff, R. L., and Wu, J.-R. A highly conserved repetitive DNA sequence,(TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl. Acad. Sci. USA, 85: 6622-6626, 1988.

Müller, R., Bravo, R., and Burckhardt, J. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature, 312: 716-720, 1984.

Nakayama, J., Saito, M., Nakamura, H., Matsuura, A., and Ishikawa, F. TLP1: a gene encoding a protein component of mammalian telomerase is a novel member of WD repeats family. Cell, 88: 875-884, 1997.

Nakayama, J. I., Tahara, H., Tahara, E., Saito, M., Ito, K., Nakamura, H., Nakanishi, T., Tahara, E., Ide, T., and Ishikawa, F. Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nature Genet., 18: 65-68, 1998.

Nielsen, G. P., Stemmer-Rachamimov, A. O., Shaw, J., Roy, J. E., and Louis, D. N. Immunohistochemical survey of p16INK4A expression in normal human adult and infant tissue. Lab. Invest., 79: 1137-1143, 1999.

Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K., and Carson, D. A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in miltiple human cancer. Nature, 368: 753-756, 1994.

Oh, S., Song, Y. H., Kim, U. J., Yim, J., and Kim, T. K. In vivo and in vitro analyses of the human telomerase(hTERT)gene in normal and tumor cells. Biochem. Biophys. Res. Commun., 263:361-365, 1999.

Oh, S., Song, Y. H., Yim, J., and Kim, T. K. Identification of Mad as a repressor of the human telomerase(hTERT)gene. Oncogene, 19: 1485-1490, 2000.

Porter, M. J., Field, J. K., Lee, J. C. K., Leung, S. F., Lo, D., and van Hasselt, C. A. Detection of the tumor suppressor gene p53 in nasopharyngeal carcinoma in Hong Kong Chinese. Anticancer Res., 14: 1357-1360, 1994.

Porter, M. J., Field, J. K., Leung, S. F., Lo, D., Lee, J. C. K., Spandidos, D. A., and van Hasselt, C. A. The detection of the c-myc and ras oncogenes in nasopharyngeal carcinoma by immunohistochemistry. Acta Otolaryngol (stockh), 114: 105-109, 1994.

Reed, A. L., Califano, J., Cairns, P., Westra, W. H., Jones, R. M., Koch, W., Ahrendt, S., Eby, Y., Sewell, D., Nawroz, H., Bartek, J., and Sidransky, D. High Frequency of p16(CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma. Cancer Res., 56: 3630-3633, 1996.

Reddy, S. P., Raslan, W. F., Gooneratne, S., Kathuria, S., and Marks, J. E. Prognostic significance of keratinization in nasopharyngeal carcinoma. Am. J. Otolaryngology, 16: 103-108, 1995.

Robson, C. N., Gnanapragasam, V., Byrne, R. L., Collinsm A. T., and Neal, D. E. Transforming growth factor-β1 up-regulates p15, p21 and p27 and blocks cell cycling in G1 in human prostate epithelium. Journal of Endocrinology, 160: 257-266, 1999.

Rosenthal, E. T., Hunt, T., and Ruderman, J. V. Selective translation of mRNA controls the pattern of protein synthesis during early development of the surf clam, Spisula solidissima. Cell, 20: 487-494, 1980.

Santoni-Rugiu, E., Jensen, M. R., and Thorgeirsson S. S. Disruption of the pRb/E2F pathway and inhibition of apoptosis are major oncogenic events in liver constitutively expressing c-myc and transforming growth factor α. Cancer Res., 58: 123-134, 1998.

Sato, Y., Itoh, F., Hareyama, M., Satoh, M., Hinoda, Y., Seto, M., Ueda, R., and Imai, K. Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma. J. Gastroenterol, 34: 486-493, 1999.

Schutte, M., Hruban, R. H., Geradts, J., Maynard, R., Hilgers, W., Rabindran, S. K., Moskaluk, C. A., Hahn, S. A., Schwarte- Waldhoff, I., Schmiegel, W., Baylin, S. B., Kern, S. E., and Herman, J. G. Abrogation of the Rb/p16 tumor-suppressive pathway in virtually all pancreatic carcinomas. Cancer Res., 57: 3126-3130, 1997.

Sellers, W. R., and Kaelin, W. G. Role of the retinoblastoma protein in the pathogenesis of human cancer. J. Clin. Oncol., 15: 3301-3312, 1997.

Shapiro, G. I., Edwards, C. D., Kobzik, L., Godleski, J., Richards, W., Sugarbaker, D. J., and Rollins, B. J. Reciprocal Rb inactivation and p16INK4 expression in primary lung cancer and cell lines. Cancer Res., 55: 505-509, 1995.

Sherr, C. J. Mammalian G1 cyclins. Cell, 73: 1059-1065, 1993.

Sun, Y., Hegamyer, G., and Colburn, N. H. Nasopharyngeal carcinoma shows no detectable retinobalstoma susceptibility gene alterations. Oncogene, 8: 791-795, 1993.

Sun. Y., Hildesheim, A., Lanier, A. E., Cao, Y., Yao, K. T., Raab-Traub, N., and Yang, C. S. No point mutation but decreased expression of the p16/mts1 tumor suppressor gene in nasopharyngeal carcinomas. Oncogene, 10: 785-788, 1995.

Takakura, M., Kyo, S., Kanaya, T., Tanaka, M., and Inoue, M. Expression of human telomerase subunits and the correlation with telomerase activity in cervical cancer. Cancer Res., 58: 1558-1561, 1998.

Tam, S. W., Shay, J. W., and Pagano, M. Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 inhibitor p16INK4. Cancer Res., 54: 5816-5820, 1994.

Teraoka, H., Sawai, M., Takase, K., Yamamoto, K., Nozaki, N., Okazaki, T., and Tsuksda, K. Expression of c-fos and c-myc in Raji Burkitt’s lymphoma cells during the progression of DMSO-induced G1 cells into S phase. Exp. Cell Res., 195: 274-276, 1991.

Toyoshima, H., and Hunter, T. p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell, 78: 67-74, 1994.

Turner, J. J., and Milliken, S. A case of keratin-positive acute myeloid leukemia: a possible role for cytokeratin 19 as a specific epithelial marker. Pathology, 32: 98-101, 2000.

van Diest, P. J., Michalides, R. J. A. M., Jannink, L., van der Valk, P.,
Peterse, H. L., de Jong, J. S., Meijer, C. J. L. M., and Baak, J. P. A. Cyclin D1 expression in invasive breast cancer correlations and prognostic value. Am. J. Pathol., 150: 705-711, 1997.

Vaziri, H., and Benchimol, S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Current Biology, 8: 279-282, 1998.

Walker, R.A., and Cowl, J. The expression of c-fos protein in human breast. J. Patho., 163: 323-327, 1991.

Wang, G. L., Lo, K. W., Tsang, K. S., Chung, N. Y. F., Tsang, Y. S., Cheung, S. T., Lee, J. C. K., and Huang, D. P. Inhibiting tumorigenic potential by restoration of p16 in nasopharyngeal carcinoma. Br. J. Cancer, 81: 1122-1126, 1999.

Wang, J., Xie, L. Y., Allan, S., Beach, D., and Hannon, G. J. Myc activates telomerase. Genes and Dev.,1769-1774, 1998.

Watson, J. D. Origins of concatemeric DNA. Nature New Biol., 239: 197-201, 1972.

Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell, 81:323-330, 1995.
Wen, J., Cong, Y. S., and Bacchetti, S. Reconstitution of wild-type or mutant telomerase activity in telomerase-negative immortal human cells. Hum. Mol. Genet., 7:1137-1141, 1998.

Whittock, N.V., Eady, R. A., and McGrath, J. A. Genomuc oragnization and amplification of the human keratin 15 and keratin 19 genes. Biochem. Biophys. Res. Commun., 267:462-465, 2000.

Wieser, R. J., Faust, D., Dietrich, C., and Oesch, F. p16INK4 mediates contact-inhibition of growth. Oncogene, 18: 277-281, 1999.

Woloschak, M., Roberts, J. L., and Post, K. c-myc, c-fos, and c-myb gene expression in human pituitary adenomas. J. Clin. Endocrinol. Metab., 79: 253-257, 1994.

Wu, F. Y. -H., Chang, N. -T., Chen, W. -J., and Juan, C. -C. Vitamin K3-induced cell cycle arrest and apoptotic cell death are accompanied by altered expression of c-fos and c-myc in nasopharyngeal carcinoma cells. Oncogene, 8: 2237-2244, 1993.

Wu, K. J., Grandori, C., Amacker, M., Simon-Vermot, N., Polack, A., Lingner, J., and Dalla-Favera, R. Direct activation of TERT transcription by c-myc. Nature Genet., 21: 220-224, 1999.

Xu, J., Menezes, J., Prasad, U., and Ahmad, A. Elevated serum levels of transforming growth factor beta 1 in Epstein-Barr virus-associated nasopharyngeal carcinoma patients. Int. J. Cancer, 84: 396-399, 1999.

Yeager, T., Stadler, W., Belair, C., Puthenveettil, J., Olopade, O., and Reznikoff, C. Increased of p16 levels correlate with pRb alterations in human urothelial cells. Cancer Res., 55: 493-497, 1995.

Yu, M. C. Nasopharyngeal carcinoma: epidemiology and dietary factors. IARC Sci. Publ., 105: 39-47, 1991.
電子全文 Fulltext
本電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。
論文使用權限 Thesis access permission:校內校外完全公開 unrestricted
開放時間 Available:
校內 Campus: 已公開 available
校外 Off-campus: 已公開 available


紙本論文 Printed copies
紙本論文的公開資訊在102學年度以後相對較為完整。如果需要查詢101學年度以前的紙本論文公開資訊,請聯繫圖資處紙本論文服務櫃台。如有不便之處敬請見諒。
開放時間 available 已公開 available

QR Code