Differential Expression of Activating Transcription Factor 5 in Human Rectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

KONG Xiangheng , MENG Wenjian , ZHOU Zongguang , LI Yuan , ZHOU Bin , WANG Rong , ZHAN Lan.

Institute of Digestive Surgery &;
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

Keywords：

Activating transcription factor 5; Rectal cancer; Quantitative real-time RT-PCR; Immunohistochemical staining

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ObjectiveTo determine the expression change of activating transcription factor 5 (ATF5) in human rectal cancer tissue, and analyze the correlation between ATF5 expression and the clinicopathologic parameters of rectal cancer. MethodsNinetytwo paired samples of rectal cancer tissue and more than 5 cm distant normal rectal tissue were obtained from inpatients between March 2009 and October 2009 in this hospital. ATF5 mRNA and protein expressions were detected by quantitative real-time RT-PCR and immunohistochemical staining. ResultsThirty-three (35.9%) cases of rectal cancer showed ATF5 mRNA overexpression; however, the expression level of ATF5 mRNA in the rectal cancer tissue was not statistically different from that in the normal rectal tissue (P=0.363). There was no evidence for the relationship between the ATF5 mRNA expression and the patients’ age, gender, histological type, tumor differentiation degree, invasive depth, lymph node metastasis, distance metastasis, or TNM stage. In contrast, the positive expression rate of ATF5 protein in the rectal cancer tissue was significantly higher than that in the normal rectal tissue (P=0.000). Moreover, the ATF5 protein expression was correlated with the tumor differentiation degree (P=0.013), but not with other clinicopathologic features (P gt;0.05). ConclusionsThe results suggest that ATF5 protein may be related to the carcinogenesis and differentiation of human rectal cancer. However, further researches are required to prove the correlation.

Citation： KONG Xiangheng,MENG Wenjian,ZHOU Zongguang,LI Yuan,ZHOU Bin,WANG Rong,ZHAN Lan.. Differential Expression of Activating Transcription Factor 5 in Human Rectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(4): 401-405. doi: Copy

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，林国乐，肖毅，等. 早期直肠癌中p53和hMLH1的表达 [J]. 中国普外基础与临床杂志, 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. 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，林国乐，肖毅，等. 早期直肠癌中p53和hMLH1的表达 [J]. 中国普外基础与临床杂志, 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Differential Expression of Activating Transcription Factor 5 in Human Rectal Cancer

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