• 四川大學華西醫(yī)院胃腸外科中心、消化外科研究室（四川成都 610041）;

目的分析人直腸癌組織中轉錄激活因子5(ATF5)的表達變化及其與直腸癌臨床病理特征的關系。方法選取四川大學華西醫(yī)院胃腸外科中心2009年3～10月期間手術切除的直腸癌及距離腫瘤5 cm以遠的正常直腸組織標本92對，分別應用實時熒光定量RTPCR和免疫組織化學染色SP法檢測ATF5 mRNA和蛋白的表達情況。結果直腸癌組織中33例(35.9%)ATF5 mRNA表達上調(diào)，但ATF5 mRNA相對表達量與正常直腸組織相比，二者間差異無統(tǒng)計學意義(P=0.363)，并且ATF5 mRNA表達與患者年齡、性別、腫瘤類型、分化程度、浸潤深度、淋巴結轉移、遠處轉移及TNM分期均無關(P gt;0.05)； 但直腸癌組織中ATF5蛋白的表達高于正常直腸組織(P=0.000)，并且其表達與腫瘤分化程度有關(P=0.013)，而與其他臨床病理因素無關(P gt;0.05)。結論ATF5蛋白的表達與直腸癌的發(fā)生和分化相關，但這種相關需要進一步的研究證明。

引用本文： 孔祥恒,孟文建,周總光,李園,周斌,王蓉,詹蘭. 轉錄激活因子5在直腸癌中的差異性表達. 中國普外基礎與臨床雜志, 2011, 18(4): 401-405. doi: 復制

1. White JH, McIllhinney RA, Wise A, et al. The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx [J]. Proc Natl Acad Sci USA, 2000, 97(25): 1396713972.
2. Persengiev SP, Devireddy LR, Green MR. Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors [J]. Genes Dev, 2002, 16(14): 18061841.
3. Angelastro JM, Ignatova TN, Kukekov VG, et al. Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons [J]. J Neurosci, 2003, 23: 45904600.
4. Angelastro JM, Mason JL, Ignatova TN, et al. Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes [J]. J Neurosci, 2005, 25(15): 38893899.
5. Wang H, Lin G, Zhang Z. ATF5 promotes cell survival through transcriptional activation of Hsp27 in H9c2 cells [J]. Cell Biol Int, 2007, 31(11): 13091315.
6. Nishioka T, Miyai Y, Haga H, et al. Novel function of transcription factor ATF5: blockade of p53dependent apoptosis induced by ionizing irradiation [J]. Cell Struct Funct, 2009, 34(1): 1722.
7. Angelastro JM, Canoll PD, Kuo J, et al. Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5 [J]. Oncogene, 2006, 25(6): 907916.
8. Monaco SE, Angelastro JM, Szabolcs M, et al. The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines [J]. Int J Cancer, 2007, 120(9): 18831890.
9. Gho JW, Ip WK, Chan KY, et al. Reexpression of transcription factor ATF5 in hepatocellular carcinoma induces G2M arrest [J]. Cancer Res, 2008, 68(16): 67436751.
10. CransVargas HN, Landaw EM, Bhatia S, et al. Expression of cyclic adenosine monophosphate responseelement binding protein in acute leukemia [J]. Blood, 2002, 99(7): 26172619.
11. Peri A, Luciani P, Conforti B, et al. Variable expression of the transcription factors cAMP response elementbinding protein and inducible cAMP early repressor in the normal adrenal cortex and in adrenocortical adenomas and carcinomas [J]. J Clin Endocrinol Metab, 2001, 86(11): 54435449.
12. Greene LA, Lee HY, Angelastro JM. The transcription factor ATF5: role in neurodevelopment and neural tumors [J]. J Neurochem, 2009, 108(1): 1122.
13. Li G, Li W, Angelastro JM, et al. Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf7 breast cancer cells [J]. Mol Cancer Res, 2009, 7(6): 933943.
14. 于新明， 林國樂， 肖毅， 等. 早期直腸癌中p53和hMLH1的表達 [J]. 中國普外基礎與臨床雜志, 2010, 17(9): 889893.
15. Pfaffl MW. A new mathematical model for relative quantification in realtime RTPCR [J]. Nucleic Acids Res, 2001, 29(9): 20032007.
16. Mygind T, Birkelund S, Birkebaek NH, et al. Determination of PCR efficiency in chelex100 purified clinical samples and comparison of realtime quantitative PCR and conventional PCR for detection of Chlamydia pneumoniae [J]. BMC Microbiol, 2002, 2: 1724.
17. Bernard PS, Wittwer CT. Realtime PCR technology for cancer diagnostics [J]. Clin Chem, 2002, 48(8): 11781185.
18. Wu CC, Shyu RY, Chou JM, et al. RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma [J]. Eur J Cancer, 2006, 42(4): 557565.
19. Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis [J]. Gene, 2001, 273(1): 111.
20. Sheng Z, Li L, Zhu LJ, et al. A genomewide RNA interference screen reveals an essential CREB3L2ATF5MCL1 survival pathway in malignant glioma with therapeutic implications [J]. Nat Med, 2010, 16(6): 671677.
21. Bhoumik A, Huang TG, Ivanov V, et al. An ATF2derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis [J]. J Clin Invest, 2002, 110(5): 643650.
22. Echlin DR, Tae HJ, Mitin N, et al. BATF function as a negative regulator of AP1 mediated transcription and blocks cellular transformation by Ras and Fos [J]. Oncogene, 2000, 19(14): 17521763.
23. Mashima T, Udagawa S, Tsuruo T. Involvement of transcriptional repressor ATF3 in acceleration of caspase protease activation during DNA damaging agentinduced apoptosis [J]. J Cell Physiol, 2001, 188(3): 352358.
24. Tanabe M, Izumi H, Ise T, et al. Activating transcription factor 4 increases the cisplatin resistance of human cancer cell lines [J]. Cancer Res, 2003, 63(24): 85928595.
25. Wei Y, Ge Y, Zhou F, et al. Identification and characterization of the promoter of human ATF5 gene [J]. J Biochem, 2010, 148(2): 171178.
26. Pati D, Meistrich ML, Plon SE. Human Cdc34 and Rad6B ubiquitinconjugating enzymes target repressors of cyclic AMPinduced transcription for proteolysis [J]. Mol Cell Biol, 1999, 19(7): 50015013.
  1. 1. White JH, McIllhinney RA, Wise A, et al. The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx [J]. Proc Natl Acad Sci USA, 2000, 97(25): 1396713972.
  2. 2. Persengiev SP, Devireddy LR, Green MR. Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors [J]. Genes Dev, 2002, 16(14): 18061841.
  3. 3. Angelastro JM, Ignatova TN, Kukekov VG, et al. Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons [J]. J Neurosci, 2003, 23: 45904600.
  4. 4. Angelastro JM, Mason JL, Ignatova TN, et al. Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes [J]. J Neurosci, 2005, 25(15): 38893899.
  5. 5. Wang H, Lin G, Zhang Z. ATF5 promotes cell survival through transcriptional activation of Hsp27 in H9c2 cells [J]. Cell Biol Int, 2007, 31(11): 13091315.
  6. 6. Nishioka T, Miyai Y, Haga H, et al. Novel function of transcription factor ATF5: blockade of p53dependent apoptosis induced by ionizing irradiation [J]. Cell Struct Funct, 2009, 34(1): 1722.
  7. 7. Angelastro JM, Canoll PD, Kuo J, et al. Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5 [J]. Oncogene, 2006, 25(6): 907916.
  8. 8. Monaco SE, Angelastro JM, Szabolcs M, et al. The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines [J]. Int J Cancer, 2007, 120(9): 18831890.
  9. 9. Gho JW, Ip WK, Chan KY, et al. Reexpression of transcription factor ATF5 in hepatocellular carcinoma induces G2M arrest [J]. Cancer Res, 2008, 68(16): 67436751.
  10. 10. CransVargas HN, Landaw EM, Bhatia S, et al. Expression of cyclic adenosine monophosphate responseelement binding protein in acute leukemia [J]. Blood, 2002, 99(7): 26172619.
  11. 11. Peri A, Luciani P, Conforti B, et al. Variable expression of the transcription factors cAMP response elementbinding protein and inducible cAMP early repressor in the normal adrenal cortex and in adrenocortical adenomas and carcinomas [J]. J Clin Endocrinol Metab, 2001, 86(11): 54435449.
  12. 12. Greene LA, Lee HY, Angelastro JM. The transcription factor ATF5: role in neurodevelopment and neural tumors [J]. J Neurochem, 2009, 108(1): 1122.
  13. 13. Li G, Li W, Angelastro JM, et al. Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf7 breast cancer cells [J]. Mol Cancer Res, 2009, 7(6): 933943.
  14. 14. 于新明， 林國樂， 肖毅， 等. 早期直腸癌中p53和hMLH1的表達 [J]. 中國普外基礎與臨床雜志, 2010, 17(9): 889893.
  15. 15. Pfaffl MW. A new mathematical model for relative quantification in realtime RTPCR [J]. Nucleic Acids Res, 2001, 29(9): 20032007.
  16. 16. Mygind T, Birkelund S, Birkebaek NH, et al. Determination of PCR efficiency in chelex100 purified clinical samples and comparison of realtime quantitative PCR and conventional PCR for detection of Chlamydia pneumoniae [J]. BMC Microbiol, 2002, 2: 1724.
  17. 17. Bernard PS, Wittwer CT. Realtime PCR technology for cancer diagnostics [J]. Clin Chem, 2002, 48(8): 11781185.
  18. 18. Wu CC, Shyu RY, Chou JM, et al. RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma [J]. Eur J Cancer, 2006, 42(4): 557565.
  19. 19. Hai T, Hartman MG. The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis [J]. Gene, 2001, 273(1): 111.
  20. 20. Sheng Z, Li L, Zhu LJ, et al. A genomewide RNA interference screen reveals an essential CREB3L2ATF5MCL1 survival pathway in malignant glioma with therapeutic implications [J]. Nat Med, 2010, 16(6): 671677.
  21. 21. Bhoumik A, Huang TG, Ivanov V, et al. An ATF2derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis [J]. J Clin Invest, 2002, 110(5): 643650.
  22. 22. Echlin DR, Tae HJ, Mitin N, et al. BATF function as a negative regulator of AP1 mediated transcription and blocks cellular transformation by Ras and Fos [J]. Oncogene, 2000, 19(14): 17521763.
  23. 23. Mashima T, Udagawa S, Tsuruo T. Involvement of transcriptional repressor ATF3 in acceleration of caspase protease activation during DNA damaging agentinduced apoptosis [J]. J Cell Physiol, 2001, 188(3): 352358.
  24. 24. Tanabe M, Izumi H, Ise T, et al. Activating transcription factor 4 increases the cisplatin resistance of human cancer cell lines [J]. Cancer Res, 2003, 63(24): 85928595.
  25. 25. Wei Y, Ge Y, Zhou F, et al. Identification and characterization of the promoter of human ATF5 gene [J]. J Biochem, 2010, 148(2): 171178.
  26. 26. Pati D, Meistrich ML, Plon SE. Human Cdc34 and Rad6B ubiquitinconjugating enzymes target repressors of cyclic AMPinduced transcription for proteolysis [J]. Mol Cell Biol, 1999, 19(7): 50015013.