• 1.四川省醫(yī)學(xué)科學(xué)院，四川省人民醫(yī)院肝膽胰外科（四川成都 610072）;;
  • 2.四川大學(xué)華西醫(yī)院肝膽胰外科（四川成都 610041）;;
  • 3.中國科學(xué)院上海生命科學(xué)研究院營養(yǎng)科學(xué)研究所（上海 200031）;

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(dá)情況和對人胰腺癌細(xì)胞株P(guān)ANC-1的生長、增殖及細(xì)胞成瘤能力的影響，并探討其作用機(jī)理。 方法以人胰腺癌細(xì)胞株P(guān)ANC-1為研究對象，構(gòu)建含RasTG基因的慢病毒轉(zhuǎn)染人胰腺癌細(xì)胞株P(guān)ANC-1，利用RNA干擾技術(shù)干擾細(xì)胞內(nèi)RasTG基因的表達(dá)，觀察干擾后PANC-1細(xì)胞的增殖、轉(zhuǎn)化和成瘤情況，并通過組織芯片技術(shù)檢測胰腺導(dǎo)管癌及其癌旁組織中RasTG蛋白的表達(dá)情況。 結(jié)果①RasTG無十分特異的組織表達(dá)譜，在腦、肝臟及腎上腺中表達(dá)相對較高； ②RasTG在胰腺導(dǎo)管癌組織中的表達(dá)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(xì)胞株P(guān)ANC-1的生長、增殖和轉(zhuǎn)化能力均下降； ④干擾RasTG基因后的人胰腺癌細(xì)胞株P(guān)ANC-1的成瘤能力明顯減弱，轉(zhuǎn)染組的成瘤體積明顯小于未轉(zhuǎn)染組(P lt;0.05)。 結(jié)論RasTG基因在動物體內(nèi)廣泛分布； RasTG在胰腺癌組織中的表達(dá)比在癌旁組織中高； 干擾RasTG基因的表達(dá)后對人胰腺癌細(xì)胞株P(guān)ANC-1的增殖、轉(zhuǎn)化和成瘤能力均有抑制作用，RasTG基因是正調(diào)節(jié)因子。

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

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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.
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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. 1. Young A, Lyons J, Miller AL, et al. Ras signaling and therapies [J]. Adv Cancer Res, 2009, 102(09): 117.
  2. 2. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth [J]. Nature, 2006, 441(7092): 424430.
  3. 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. 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. 5. Lin SG, Zhang R, Wang JQ. RNA interference technique and the using [J]. J Mod Lab Med, 2008, 23(4): 8386.
  6. 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. 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. 8. de Braud F, Cascinu S, Gatta G. Cancer of pancreas [J]. Crit Rev Oncol Hematol, 2004, 50(2): 147155.
  9. 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. 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. 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. 12. Wakeman CJ, Martin IG, Robertson RW, et al. Pancreatic cancer: management and survival [J]. ANZ J Surg, 2004, 74(11): 941944.
  13. 13. Takhar AS, Palaniappan P, Dhingsa R, et al. Recent developments in diagnosis of pancreatic cancer [J]. BMJ, 2004, 329(7467): 668673.
  14. 14. Sarkar FH, Banerjee S, Li Y. Pancreatic cancer: pathogenesis, prevention and treatment [J/OL]. Toxicol Appl Pharmacol, 2007, 224(3): 326336.
  15. 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. 16. Rozenblum E, Schutte M, Goggins M, et al. Tumorsuppressive pathways in pancreatic carcinoma [J]. Cancer Res, 1997, 57(9): 17311734.
  17. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.