RasTG基因與胰腺癌的相關性研究_《中國普外基礎與臨床雜志》

作者：

龔軍 ¹ , 向光明 ² , 鄭振江 ² , 譚春露 ² , 劉續寶 ² , 陳雁 ³

1.四川省醫學科學院，四川省人民醫院肝膽胰外科（四川成都 610072）;;
2.四川大學華西醫院肝膽胰外科（四川成都 610041）;;
3.中國科學院上海生命科學研究院營養科學研究所（上海 200031）;

關鍵詞：

Ras蛋白 RasTG基因胰腺癌

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目的體外觀察高爾基嵌合Ras基因（RasTG基因）在胰腺癌組織中的表達情況和對人胰腺癌細胞株PANC-1的生長、增殖及細胞成瘤能力的影響，并探討其作用機理。方法以人胰腺癌細胞株PANC-1為研究對象，構建含RasTG基因的慢病毒轉染人胰腺癌細胞株PANC-1，利用RNA干擾技術干擾細胞內RasTG基因的表達，觀察干擾后PANC-1細胞的增殖、轉化和成瘤情況，并通過組織芯片技術檢測胰腺導管癌及其癌旁組織中RasTG蛋白的表達情況。結果①RasTG無十分特異的組織表達譜，在腦、肝臟及腎上腺中表達相對較高； ②RasTG在胰腺導管癌組織中的表達明顯高于癌旁組織（P lt;0.05）； ③干擾RasTG基因后的人胰腺癌細胞株PANC-1的生長、增殖和轉化能力均下降； ④干擾RasTG基因后的人胰腺癌細胞株PANC-1的成瘤能力明顯減弱，轉染組的成瘤體積明顯小于未轉染組(P lt;0.05)。結論RasTG基因在動物體內廣泛分布； RasTG在胰腺癌組織中的表達比在癌旁組織中高；干擾RasTG基因的表達后對人胰腺癌細胞株PANC-1的增殖、轉化和成瘤能力均有抑制作用，RasTG基因是正調節因子。

引用本文： 龔軍,向光明,鄭振江,譚春露,劉續寶,陳雁. RasTG基因與胰腺癌的相關性研究. 中國普外基礎與臨床雜志, 2011, 18(11): 1169-1174. doi: 復制

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15.	Wright WE, Shay JW, Piatyszek MA. Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity [J]. Nucleic Acids Res, 1995, 23(18): 37943795.
16.	Rozenblum E, Schutte M, Goggins M, et al. Tumorsuppressive pathways in pancreatic carcinoma [J]. Cancer Res, 1997, 57(9): 17311734.
17.	Chiu VK, Bivona T, Hach A, et al. Ras signalling on the endoplasmic reticulum and the Golgi [J]. Nat Cell Biol, 2002, 4(5): 343350.
18.	Hirai H, Okabe T, Anraku Y, et al. Activation of the cKras oncogene in a human pancreas carcinoma [J]. Biochem Biophys Res Commun, 1985, 127(1): 168174.
19.	Matsubayashi H, Watanabe H, Yamaguchi T, et al. Multiple Kras mutations in hyperplasia and carcinoma in cases of human pancreatic carcinoma [J]. Jpn J Cancer Res, 1999, 90(8): 841848.
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21.	Westra WH, Sturm P, Drillenburg P, et al. Kras oncogene mutations in osteoclastlike giant cell tumors of the pancreas and liver: genetic evidence to support origin from the duct epithelium [J]. Am J Surg Pathol, 1998, 22(10): 12471254.
22.	Tateishi K, Tada M, Yamagata M, et al. High proportion of mutant Kras gene in pancreatic juice of patients with pancreatic cystic lesions [J]. Gut, 1999, 45(5): 737740.
23.	Kimura W, Zhao B, Futakawa N, et al. Significance of Kras codon 12 point mutation in pancreatic juice in the diagnosis of carcinoma of the pancreas [J]. Hepatogastroenterology, 1999, 46(25): 532539.
24.	Ebert MP, Hoffmann J, SchneiderStock R, et al. Analysis of Kras gene mutations in rare pancreatic and ampullary tumours [J]. Eur J Gastroenterol Hepatol, 1998, 10(12): 10251029.
25.	Mora J, Puig P, Boadas J, et al. Kras gene mutations in the diagnosis of fineneedle aspirates of pancreatic masses: prospective study using two techniques with different detection limits [J]. Clin Chem, 1998, 44(11): 22432248.
26.	Pabst B, Arps S, Binmoeller K, et al. Analysis of Kras mutations in pancreatic tissue after fine needle aspirates [J]. Anticancer Res, 1999, 19(4A): 24812483.
27.	Singh A, Greninger P, Rhodes D, et al. A gene expression signature associated with “KRas addiction” reveals regulators of EMT and tumor cell survival [J]. Cancer Cell, 2009, 15(6): 489500.

1. Young A, Lyons J, Miller AL, et al. Ras signaling and therapies [J]. Adv Cancer Res, 2009, 102(09): 117.
2. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth [J]. Nature, 2006, 441(7092): 424430.
3. Tang YT, Hu T, Arterburn M, et al. PAQR proteins: a novel membrane receptor family defined by an ancient 7transmembrane pass motif [J]. J Mol Evol, 2005, 61(3): 372380.
4. Zhu Y, Bond J, Thomas P. Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor [J]. Proc Natl Acad Sci USA, 2003, 100(5): 22372242.
5. Lin SG, Zhang R, Wang JQ. RNA interference technique and the using [J]. J Mod Lab Med, 2008, 23(4): 8386.
6. Bivona TG, Pérez De Castro I, Ahearn IM, et al. Phospholipase cgamma activates Ras on the golgi apparatus by means of RasGRP1 [J]. Nature, 2003, 424(6949): 694698.
7. Rehli M, Krause SW, Schwarzfischer L, et al. Molecular cloning of a novel macrophage maturationassociated transcript encoding a protein with several potential transmembrane domains [J]. Biochem Biophys Res Commun, 1995, 217(2): 661667.
8. de Braud F, Cascinu S, Gatta G. Cancer of pancreas [J]. Crit Rev Oncol Hematol, 2004, 50(2): 147155.
9. Mann O, Strate T, Schneider C, et al. Surgery for advanced and metastatic pancreatic cancer—current state and perspectives [J]. Anticancer Res, 2006, 26(1B): 681686.
10. Riall TS, Nealon WH, Goodwin JS, et al. Pancreatic cancer in the general population: Improvements in survival over the last decade [J]. J Gastrointest Surg, 2006, 10(9): 12121223.
11. Wenger FA, Peter F, Zieren J, et al. Prognosis factors in carcinoma of the head of the pancreas [J]. Dig Surg, 2000, 17(1): 2935.
12. Wakeman CJ, Martin IG, Robertson RW, et al. Pancreatic cancer: management and survival [J]. ANZ J Surg, 2004, 74(11): 941944.
13. Takhar AS, Palaniappan P, Dhingsa R, et al. Recent developments in diagnosis of pancreatic cancer [J]. BMJ, 2004, 329(7467): 668673.
14. Sarkar FH, Banerjee S, Li Y. Pancreatic cancer: pathogenesis, prevention and treatment [J/OL]. Toxicol Appl Pharmacol, 2007, 224(3): 326336.
15. Wright WE, Shay JW, Piatyszek MA. Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity [J]. Nucleic Acids Res, 1995, 23(18): 37943795.
16. Rozenblum E, Schutte M, Goggins M, et al. Tumorsuppressive pathways in pancreatic carcinoma [J]. Cancer Res, 1997, 57(9): 17311734.
17. Chiu VK, Bivona T, Hach A, et al. Ras signalling on the endoplasmic reticulum and the Golgi [J]. Nat Cell Biol, 2002, 4(5): 343350.
18. Hirai H, Okabe T, Anraku Y, et al. Activation of the cKras oncogene in a human pancreas carcinoma [J]. Biochem Biophys Res Commun, 1985, 127(1): 168174.
19. Matsubayashi H, Watanabe H, Yamaguchi T, et al. Multiple Kras mutations in hyperplasia and carcinoma in cases of human pancreatic carcinoma [J]. Jpn J Cancer Res, 1999, 90(8): 841848.
20. Okai T, Watanabe H, Yamaguchi Y, et al. EUS and Kras analysis of pure pancreatic juice collected via a duodenoscope after secretin stimulation for diagnosis of pancreatic mass lesion: a prospective study [J]. Gastrointest Endosc, 1999, 50(6): 797803.
21. Westra WH, Sturm P, Drillenburg P, et al. Kras oncogene mutations in osteoclastlike giant cell tumors of the pancreas and liver: genetic evidence to support origin from the duct epithelium [J]. Am J Surg Pathol, 1998, 22(10): 12471254.
22. Tateishi K, Tada M, Yamagata M, et al. High proportion of mutant Kras gene in pancreatic juice of patients with pancreatic cystic lesions [J]. Gut, 1999, 45(5): 737740.
23. Kimura W, Zhao B, Futakawa N, et al. Significance of Kras codon 12 point mutation in pancreatic juice in the diagnosis of carcinoma of the pancreas [J]. Hepatogastroenterology, 1999, 46(25): 532539.
24. Ebert MP, Hoffmann J, SchneiderStock R, et al. Analysis of Kras gene mutations in rare pancreatic and ampullary tumours [J]. Eur J Gastroenterol Hepatol, 1998, 10(12): 10251029.
25. Mora J, Puig P, Boadas J, et al. Kras gene mutations in the diagnosis of fineneedle aspirates of pancreatic masses: prospective study using two techniques with different detection limits [J]. Clin Chem, 1998, 44(11): 22432248.
26. Pabst B, Arps S, Binmoeller K, et al. Analysis of Kras mutations in pancreatic tissue after fine needle aspirates [J]. Anticancer Res, 1999, 19(4A): 24812483.
27. Singh A, Greninger P, Rhodes D, et al. A gene expression signature associated with “KRas addiction” reveals regulators of EMT and tumor cell survival [J]. Cancer Cell, 2009, 15(6): 489500.

《中國普外基礎與臨床雜志》

RasTG基因與胰腺癌的相關性研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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《中國普外基礎與臨床雜志》

RasTG基因與胰腺癌的相關性研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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