• 【作者單位】成都軍區(qū)總醫(yī)院全軍普通外科中心（成都610083）;

目的了解survivin基因在腫瘤研究中的作用。方法采用文獻回顧的方法，對survivin的分子結(jié)構(gòu)、功能、作用機理、組織分布及其在腫瘤治療中的作用進行綜述。結(jié)果survivin作為凋亡抑制蛋白(inhibitor of apoptosis protein,IAP)家族的新成員，獨立于bcl2，表達于幾乎所有常見的人類惡性腫瘤組織，其表達與多種腫瘤患者預(yù)后不良密切相關(guān)。survivin通過直接抑制凋亡信號傳導(dǎo)途徑中最下游的效應(yīng)分子caspase3的活性而發(fā)揮其抑凋亡作用。抑制survivin的表達，以阻斷其抑凋亡作用，可以達到治療腫瘤的目的。結(jié)論survivin廣泛表達于多種人類惡性腫瘤組織，可作為預(yù)后不良的重要指標，并可作為抗腫瘤治療中重要的新靶點。

引用本文： 陳濤,綜述 田伏洲,審校. survivin基因與腫瘤研究進展. 中國普外基礎(chǔ)與臨床雜志, 2002, 9(5): 364-366. doi: 復(fù)制

1. Adida C, Crotty PL, McGrath J, et al. Developmentally regulated expression of the novel cancer antiapoptosis gene survivin in human and mouse proliferation [J]. Am J Pathol,1998； 152(1)∶43.
2. Konno R, Yamakawa H, Utsunomiya H, et al. Expression of survivin and bcl2 in the normal human endometrium [J]. Mol Hum Reprod,2000； 6(6)∶529.
3. Uren AG, Beilharz T, O’connell MJ, et al. Role for yeast inhibitor of apoptosis (IAP)like proteins in cell division [J]. Proc Natl Acad Sci USA, 1999； 96(18)∶10170.
4. Fraser AG, James C, Evan GI, et al. Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR1 plays a conserved role in cytokinesis [J]. Curr Biol, 1999； 9(6)∶292.
5. Takahashi R, Deveraux Q, Tamm I, et al. A single BIR domain of XIAP sufficient for inhibiting caspases [J]. J Biol Chem, 1998； 273(14)∶7787.
6. Li F, Altieri DC. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycledependent expression [J]. Cancer Res, 1999； 59(13)∶3143.
7. Conway EM, Pollefeyt S, Cornelissen J, et al. Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions [J]. Blood, 2000； 95(4)∶1435.
8. Kobayashi K, Hatano M, Otaki M, et al. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation [J]. Proc Natl Acad Sci USA, 1999； 96(4)∶1457.
9. Ambrosini G, Adida C, Altieri DC, et al. A novel antiapoptosis gene, survivin expressed in cancer and lymphoma [J]. Nat Med, 1997； 3(8)∶917.
10. Verdecia MA, Huang H, Dutil E, et al. Structure of the human antiapoptotic protein survivin reveals a dimeric arrangement [J]. Nat Struct Biol,2000； 7(7)∶602.
11. Mahotka C, Wenzel M, Springer E, et al. survivindeltaEx3 and survivin2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties [J]. Cancer Res, 1999； 59(24)∶6097.
12. Tamm I, Wang Y, Sausville E, et al. IAPfamily protein survivin inhibits caspase activity and apoptosis induced by Fas(CD95), Bax, caspases, and anticancer drugs [J]. Cancer Res, 1998； 58(23)∶5315.
13. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDK4to resist Fasmediated cell death [J]. Oncogene, 2000； 19(10)∶1346.
14. Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with CDK4/p16(INK4a) and CDK2/cyclin E complex activation [J]. Oncogene, 2000； 19(29)∶3225.
15. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin [J]. Nature, 1998； 396(6711)∶580.
16. Ito T, Shiraki K, Sugimoto K, et al. Survivin promotes cell proliferation in human hepatocellular carcinoma [J]. Hepatology, 2000； 31(5)∶1080.
17. Sarela AI, Macadam RC, Farmery SM, et al. Expression of the antiapoptosis gene, survivin, predicts death from recurrent colorectal carcinoma [J]. Gut, 2000； 46(5)∶645.
18. Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer [J]. Cancer Res, 1998； 58(22)∶5071.
19. Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas [J]. Clin Cancer Res, 2000； 6(1)∶127.
20. Monzo M, Roseu R, Felip E, et al. A novel antiapoptosis gene:Reexpression of survivin messenger RNA as a prognosis marker in nonsmallcell lung cancer [J]. J Clin Oncol, 1999； 17(7)∶2100.
21. Lu CD, Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas [J]. Cancer Res, 1998； 58(9)∶1808.
22. Saitoh Y, Yaginuma Y, Ishikawa M. Analysis of bcl2, Bax and survivin genes in uterine cancer [J]. Int J Oncol, 1999； 15(1)∶137.
23. Islam A, Kageyama H, Takada N, et al. High expression of survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma [J]. Oncogene, 2000； 19(5)∶617.
24. Grossman D, McNiff JM, Li F, et al. Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line [J]. Lab Invest, 1999； 79(9)∶1121.
25. Swana HS, Grossman D, Anthony JN, et al. Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer [J]. N Engl J Med, 1999； 341(6)∶452.
26. Tran J, Rak J, Sheehan C, et al. Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells [J]. Biochem Biophys Res Commun, 1999； 264(3)∶781.
27. Papapetropoulos A, Fulton D, Mahboubi K, et al. Angiopoietin1 inhibits endothelial cell apoptosis via the Akt/survivin pathway [J]. J Biol Chem, 2000； 275(13)∶9102.
28. O’connor DS, Schechner JS, Adida C. Control of apoptosis during angiogenesis by survivin expression in endothelial cells [J]. Am J Pathol, 2000； 156(2)∶393.
29. Buolamwini JK. Novel anticancer drug discovery [J]. Curr Opin Chem Biol, 1999； 3(4)∶500.
30. Olie RA, SimoesWust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy [J]. Cancer Res, 2000； 60(11)∶2805.
31. Chen J, Wu W, Tahir SK, et al. Downregulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorageindependent growth [J]. Neoplasia, 2000； 2(3)∶235.
32. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting [J]. J Biol Chem, 1998； 273(18)∶11177.
  1. 1. Adida C, Crotty PL, McGrath J, et al. Developmentally regulated expression of the novel cancer antiapoptosis gene survivin in human and mouse proliferation [J]. Am J Pathol,1998； 152(1)∶43.
  2. 2. Konno R, Yamakawa H, Utsunomiya H, et al. Expression of survivin and bcl2 in the normal human endometrium [J]. Mol Hum Reprod,2000； 6(6)∶529.
  3. 3. Uren AG, Beilharz T, O’connell MJ, et al. Role for yeast inhibitor of apoptosis (IAP)like proteins in cell division [J]. Proc Natl Acad Sci USA, 1999； 96(18)∶10170.
  4. 4. Fraser AG, James C, Evan GI, et al. Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR1 plays a conserved role in cytokinesis [J]. Curr Biol, 1999； 9(6)∶292.
  5. 5. Takahashi R, Deveraux Q, Tamm I, et al. A single BIR domain of XIAP sufficient for inhibiting caspases [J]. J Biol Chem, 1998； 273(14)∶7787.
  6. 6. Li F, Altieri DC. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycledependent expression [J]. Cancer Res, 1999； 59(13)∶3143.
  7. 7. Conway EM, Pollefeyt S, Cornelissen J, et al. Three differentially expressed survivin cDNA variants encode proteins with distinct antiapoptotic functions [J]. Blood, 2000； 95(4)∶1435.
  8. 8. Kobayashi K, Hatano M, Otaki M, et al. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation [J]. Proc Natl Acad Sci USA, 1999； 96(4)∶1457.
  9. 9. Ambrosini G, Adida C, Altieri DC, et al. A novel antiapoptosis gene, survivin expressed in cancer and lymphoma [J]. Nat Med, 1997； 3(8)∶917.
  10. 10. Verdecia MA, Huang H, Dutil E, et al. Structure of the human antiapoptotic protein survivin reveals a dimeric arrangement [J]. Nat Struct Biol,2000； 7(7)∶602.
  11. 11. Mahotka C, Wenzel M, Springer E, et al. survivindeltaEx3 and survivin2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties [J]. Cancer Res, 1999； 59(24)∶6097.
  12. 12. Tamm I, Wang Y, Sausville E, et al. IAPfamily protein survivin inhibits caspase activity and apoptosis induced by Fas(CD95), Bax, caspases, and anticancer drugs [J]. Cancer Res, 1998； 58(23)∶5315.
  13. 13. Suzuki A, Ito T, Kawano H, et al. Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDK4to resist Fasmediated cell death [J]. Oncogene, 2000； 19(10)∶1346.
  14. 14. Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with CDK4/p16(INK4a) and CDK2/cyclin E complex activation [J]. Oncogene, 2000； 19(29)∶3225.
  15. 15. Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by survivin [J]. Nature, 1998； 396(6711)∶580.
  16. 16. Ito T, Shiraki K, Sugimoto K, et al. Survivin promotes cell proliferation in human hepatocellular carcinoma [J]. Hepatology, 2000； 31(5)∶1080.
  17. 17. Sarela AI, Macadam RC, Farmery SM, et al. Expression of the antiapoptosis gene, survivin, predicts death from recurrent colorectal carcinoma [J]. Gut, 2000； 46(5)∶645.
  18. 18. Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer [J]. Cancer Res, 1998； 58(22)∶5071.
  19. 19. Tanaka K, Iwamoto S, Gon G, et al. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas [J]. Clin Cancer Res, 2000； 6(1)∶127.
  20. 20. Monzo M, Roseu R, Felip E, et al. A novel antiapoptosis gene:Reexpression of survivin messenger RNA as a prognosis marker in nonsmallcell lung cancer [J]. J Clin Oncol, 1999； 17(7)∶2100.
  21. 21. Lu CD, Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas [J]. Cancer Res, 1998； 58(9)∶1808.
  22. 22. Saitoh Y, Yaginuma Y, Ishikawa M. Analysis of bcl2, Bax and survivin genes in uterine cancer [J]. Int J Oncol, 1999； 15(1)∶137.
  23. 23. Islam A, Kageyama H, Takada N, et al. High expression of survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma [J]. Oncogene, 2000； 19(5)∶617.
  24. 24. Grossman D, McNiff JM, Li F, et al. Expression of the apoptosis inhibitor, survivin, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line [J]. Lab Invest, 1999； 79(9)∶1121.
  25. 25. Swana HS, Grossman D, Anthony JN, et al. Tumor content of the antiapoptosis molecule survivin and recurrence of bladder cancer [J]. N Engl J Med, 1999； 341(6)∶452.
  26. 26. Tran J, Rak J, Sheehan C, et al. Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells [J]. Biochem Biophys Res Commun, 1999； 264(3)∶781.
  27. 27. Papapetropoulos A, Fulton D, Mahboubi K, et al. Angiopoietin1 inhibits endothelial cell apoptosis via the Akt/survivin pathway [J]. J Biol Chem, 2000； 275(13)∶9102.
  28. 28. O’connor DS, Schechner JS, Adida C. Control of apoptosis during angiogenesis by survivin expression in endothelial cells [J]. Am J Pathol, 2000； 156(2)∶393.
  29. 29. Buolamwini JK. Novel anticancer drug discovery [J]. Curr Opin Chem Biol, 1999； 3(4)∶500.
  30. 30. Olie RA, SimoesWust AP, Baumann B, et al. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy [J]. Cancer Res, 2000； 60(11)∶2805.
  31. 31. Chen J, Wu W, Tahir SK, et al. Downregulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorageindependent growth [J]. Neoplasia, 2000； 2(3)∶235.
  32. 32. Ambrosini G, Adida C, Sirugo G, et al. Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting [J]. J Biol Chem, 1998； 273(18)∶11177.