臺灣博碩士論文加值系統

食道癌的早期症狀並不明顯，通常是要到腫瘤長到一個程度、引起症狀，才會被發現，而通常此時大部分病人已是癌症晚期了！所以找到一些相關的分子，可以讓我們早期去診斷食道癌或是評估預後，是非常重要的。
PEG10是一個由父親的對偶基因所表現的基因，已被研究出在肝癌有過量表現．而且也發現在老鼠肝再生的G2/M phase，PEG10的表現會增加。我們實驗室利用反轉錄作用－聚合酵素連鎖反應，發現PEG10在食道癌病人的腫瘤組織大量表現，但是在鄰近正常組織的表現為很低或偵測不到，而且在人類食道癌細胞株有過度表現的情形(與食道癌病人的鄰近正常組織比較)。利用免疫組織化學染色，偵測到PEG10在食道癌病人組織的細胞核和細胞質有強烈表現。進一步測試PEG10基因對食道癌細胞生長的影響，我們用會表現PEG10的腺病毒去感染食道癌細胞株CE48T/VGH，發現和沒有被感染的細胞或被感染不帶基因的腺病毒的細胞比較，被會表現PEG10的腺病毒感染的細胞，在第二天時，出現促進細胞生長的現象，且有統計上顯著差異，而且這種現象一直持續到第四天，在CE81T/VGH細胞，PEG10也可以促進細胞的生長。而在CE48T/VGH細胞，PEG10無法抑制食道癌臨床用藥Cisplatin所造成的細胞毒殺作用，此外，PEG10蛋白質並沒有ubiquitination的現象，另外我們也發現將CE81T/VGH處理TGF-β(1 ng/ml)時，可以促進PEG10蛋白質的表現，而有關PEG10如何促進細胞生長的機制，則還需要進一步的研究．

關鍵字：食道癌、PEG10

PEG10 is a paternally expressed gene, which was reported to be overexpressed in hepatoma. By RT-PCR, we identified that PEG10 was highly expressed in the human esophageal carcinoma tissues, but was very low or even undetectable in the adjacent normal tissues. By immunohistochemical staining, strong nuclear and cytoplasmic staining of PEG10 was detected in esophageal carcinoma tissues. To test the effects of PEG10 gene on growth of esophageal carcinoma cells, we infected esophageal carcinoma cell lines with a replication-deficient adenovirus expressing PEG10 (Ad-PEG10). The data revealed that PEG10 promoted cell proliferation in CE48T/VGH and CE81T/VGH cells. While PEG10 did not affect the cytotoxicity of treat with cisplatin in CE48T/VGH cells. In addition, the degradation of PEG10 protein doesn’t go through the ubiquitin-proteasome pathway. And we also found treatment of CE81T/VGH cells with TGF-β(1 ng/ml) resulted in increase in PEG10 protein expression by Western blotting. The mechanisms of PEG10 on promoting cell proliferation still needs further investigation.

Key words：esophageal carcinoma、PEG10

Blot WJ, McLaughlin JK. The changing epidemiology of esophageal cancer. Semin Oncol 1999;26:Suppl 15:2-8.
Blot WJ. Esophageal cancer trends and risk factors. Semin Oncol 21: 403-410;1994.
Brown LM, Hoover R, Silverman D, et al. Excess incidence of squamous cell esophageal cancer among US Black men: role of social class and other risk factors. Am J Epidemiol 2001;153:114-122.
Chen SC, Chou CK, Wong FH, Chang CM, Hu CP. Overexpression of epidermal growth factor and insulin-like growth factor-I receptors and autocrine stimulation in human esophageal carcinoma cells. Cancer Res. 1991;51(7):1898-903.
Chow WH, Blot WJ, Vaughan TL, et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 1998;90:150-155.
Daly JM, Fry WA, Little AG, et al. Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg 2000;190:562-572.
de Martel C, Llosa AE, Farr SM, Friedman GD, Vogelman JH, Orentreich N, Corley DA, Parsonnet J. J Infect Dis. 2005;191(5):761-7.
Farrow DC, Vaughan TL, Sweeney C, et al. Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer. Cancer Causes Control 2000;11:231-238.
Hu CP, Hsieh HG, Chien KY, Wang PY, Wang CI, Chen CY, Lo SJ, Wuu KD, Chang CM. Biologic properties of three newly established human esophageal carcinoma cell lines. J Natl Cancer Inst. 1984;72(3):577-83.
Kikuno, R., Nagase, T., Ishikawa, K., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. 1999 DNA Res. 6, 197-205.
Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825-831.
Liu YC, Chen SC, Chang C, Leu CM, Hu CP. Platelet-derived growth factor is an autocrine stimulator for the growth and survival of human esophageal carcinoma cell lines. Exp Cell Res. 1996;228(2):206-11.
Liu YC, Leu CM, Wong FH, Fong WS, Chen SC, Chang C, Hu CP. Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells. J Biomed Sci. 2002;9(6 Pt 2):665-74.
Lux A, Beil C, Majety M, Barron S, Gallione CJ, Kuhn HM, Berg JN, Kioschis P, Marchuk DA, Hafner M. Human retroviral gag- and gag-pol-like proteins interact with the transforming growth factor-beta receptor activin receptor-like kinase 1. J Biol Chem. 2005;280(9):8482-93.
Okabe H, Satoh S, Furukawa Y, Kato T, Hasegawa S, Nakajima Y, Yamaoka Y, Nakamura Y. Involvement of PEG10 in human hepatocellular carcinogenesis through interaction with SIAH1. Cancer Res. 2003;63(12):3043-8.
Ono R, Kobayashi S, Wagatsuma H, Aisaka K, Kohda T, Kaneko-Ishino T, Ishino F. A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics. 2001;73(2):232-7.
Ono R, Shiura H, Aburatani H, Kohda T, Kaneko-Ishino T, Ishino F. Identification of a large novel imprinted gene cluster on mouse proximal chromosome 6. Genome Res. 2003;13(7):1696-705.
Ries LAG, Eisner MP, Kosary C, et al., eds. SEER cancer statistics review, 1973-1999. Bethesda, Md.: National Cancer Institute, 2002.
Romeo Y, Cameron AJ, Schaid DJ, et al. Barrett's esophagus: prevalence in symptomatic relatives. Am J Gastroenterol 2002;97:1127-1132.
Shaheen N, Ransohoff DF. Gastroesophageal reflux, Barrett esophagus, and esophageal cancer: scientific review. JAMA 2002;287:1972-1981.
Shigemoto, K., Brennan, J., Walls, E., Watson, C. J., Stott, D., Rigby, P. W., and Reith, A. D. 2001 Nucleic Acids Res. 29, 4079-4088
Terry P, Lagergren J, Hansen H, Wolk A, Nyren O. Fruit and vegetable consumption in the prevention of oesophageal and cardia cancers. Eur J Cancer Prev 2001;10:365-369.
Tsou AP, Chuang YC, Su JY, Yang CW, Liao YL, Liu WK, Chiu JH, Chou CK. Overexpression of a novel imprinted gene, PEG10, in human hepatocellular carcinoma and in regenerating mouse livers. J Biomed Sci. 2003;10(6 Pt 1):625-35.
Wheeler TC, Chin LS, Li Y, Roudabush FL, Li L. Regulation of synaptophysin degradation by mammalian homologues of seven in absentia. J Biol Chem. 2002;277(12):10273-82.
Wu AH, Wan P, Bernstein L. A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinoma of the stomach and esophagus (United States). Cancer Causes Control 2001;12:721-732.