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Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer

Authors: Qingsong Sheng, Ying Zhang, Rui Wang, Jianfang Zhang, Biliang Chen, Jian Wang, Wei Zhang, Xiaoyan Xin

Published in: Medical Oncology | Issue 2/2012

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Abstract

Cytoplasmic localization of apurinic/apyrimidinic endonuclease 1 (APE1) correlates with different tumorigenic processes and poor prognosis in several cancer types. However, rare investigation into the prognosis value of cytoplasmic localization of APE1 was provided in ovarian cancer. The present study examined for the first time the cytoplasmic localization of APE1 in epithelial ovarian cancer (EOC) by immunohistochemistry. The relationship between cytoplasmic localization of APE1 and clinicopathological parameters, as well as the correlation between cytoplasmic localization of APE1 and prognosis, was investigated. We found that cytoplasmic positivity was significantly higher in EOCs with low tumor differentiation (P = 0.002) and was significantly higher in advanced Federation International of Gynecology and Obstetrics (FIGO) stage (III + IV) patients compared to that in early FIGO stage (I + II) patients (40.7% vs. 11.8%; P = 0.002). No significant difference was observed in APE1 pattern referring to age, tumor size, family history, histological type, ascites, and lymphatic metastasis (P > 0.05). In addition, a lower survival rate was found in patients with cytoplasmic positive localization of APE1 compared to that in patients with cytoplasmic negative localization (P < 0.05). All these findings suggest that cytoplasmic localization of APE1 is associated with tumor progression and might be a valuable prognostic marker for EOC.
Literature
1.
go back to reference Auersperg N, Wong AS, Choi KC, et al. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev. 2001;22(2):255–88.PubMedCrossRef Auersperg N, Wong AS, Choi KC, et al. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev. 2001;22(2):255–88.PubMedCrossRef
2.
go back to reference Cheng X, Young TW, Mei FC. Proteomics analyses of ovarian cancer using genetically defined human ovarian cancer models. Front Biosci. 2007;125:166–74. Cheng X, Young TW, Mei FC. Proteomics analyses of ovarian cancer using genetically defined human ovarian cancer models. Front Biosci. 2007;125:166–74.
3.
4.
go back to reference Dianov GL, Sleeth KM, Dianova II, et al. Repair of abasic sites in DNA. Mutat Res. 2003;531(1–2):157–63.PubMed Dianov GL, Sleeth KM, Dianova II, et al. Repair of abasic sites in DNA. Mutat Res. 2003;531(1–2):157–63.PubMed
5.
go back to reference Diamond DA, Parsian A, Hunt CR, et al. Redox factor-1 (Ref-1) mediates the activation of AP-1 in HeLa and NIH 3T3 cells in response to heat shock. J Biol Chem. 1999;274(24):16959–64.PubMedCrossRef Diamond DA, Parsian A, Hunt CR, et al. Redox factor-1 (Ref-1) mediates the activation of AP-1 in HeLa and NIH 3T3 cells in response to heat shock. J Biol Chem. 1999;274(24):16959–64.PubMedCrossRef
6.
go back to reference Hirota K, Matsui M, Iwata S, et al. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci USA. 1997;94(8):3633–8.PubMedCrossRef Hirota K, Matsui M, Iwata S, et al. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc Natl Acad Sci USA. 1997;94(8):3633–8.PubMedCrossRef
7.
go back to reference Tell G, Damante G, Caldwell D, et al. The intracellular localization of APE1/Ref-1: more than a passive phenomenon? Antioxid Redox Signal. 2005;7(3–4):367–84.PubMedCrossRef Tell G, Damante G, Caldwell D, et al. The intracellular localization of APE1/Ref-1: more than a passive phenomenon? Antioxid Redox Signal. 2005;7(3–4):367–84.PubMedCrossRef
8.
go back to reference Evans AR, Limp-Foster M, Kelley MR. Going APE over ref-1. Mutat Res. 2000;461(2):83–108.PubMed Evans AR, Limp-Foster M, Kelley MR. Going APE over ref-1. Mutat Res. 2000;461(2):83–108.PubMed
9.
go back to reference Noike T, Miwa S, Soeda J, et al. Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer. Hum Pathol. 2008;39(2):201–8.PubMedCrossRef Noike T, Miwa S, Soeda J, et al. Increased expression of thioredoxin-1, vascular endothelial growth factor, and redox factor-1 is associated with poor prognosis in patients with liver metastasis from colorectal cancer. Hum Pathol. 2008;39(2):201–8.PubMedCrossRef
10.
go back to reference Kakolyris S, Kaklamanis L, Engels K, et al. Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis. Br J Cancer. 1998;77(7):1169–73.PubMedCrossRef Kakolyris S, Kaklamanis L, Engels K, et al. Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis. Br J Cancer. 1998;77(7):1169–73.PubMedCrossRef
11.
go back to reference Qing Y, Wang D, Lei X, et al. The expression of APE1 and its correlation with prognostic significance after 252Cf radiotherapy in cervical cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009;40(1):125–8.PubMed Qing Y, Wang D, Lei X, et al. The expression of APE1 and its correlation with prognostic significance after 252Cf radiotherapy in cervical cancer. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009;40(1):125–8.PubMed
12.
go back to reference Di Maso V, Avellini C, Croce LS, et al. Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: possible prognostic significance. Mol Med. 2007;13(1–2):89–96.PubMed Di Maso V, Avellini C, Croce LS, et al. Subcellular localization of APE1/Ref-1 in human hepatocellular carcinoma: possible prognostic significance. Mol Med. 2007;13(1–2):89–96.PubMed
13.
go back to reference Puglisi F, Aprile G, Minisini AM, et al. Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas. Anticancer Res. 2001;21(6A):4041–9.PubMed Puglisi F, Aprile G, Minisini AM, et al. Prognostic significance of Ape1/ref-1 subcellular localization in non-small cell lung carcinomas. Anticancer Res. 2001;21(6A):4041–9.PubMed
14.
go back to reference Al-Attar A, Gossage L, Fareed KR, et al. Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers. Br J Cancer. 2010;102(4):704–9.PubMedCrossRef Al-Attar A, Gossage L, Fareed KR, et al. Human apurinic/apyrimidinic endonuclease (APE1) is a prognostic factor in ovarian, gastro-oesophageal and pancreatico-biliary cancers. Br J Cancer. 2010;102(4):704–9.PubMedCrossRef
15.
go back to reference Russo D, Arturi F, Bulotta S, et al. ApeI/Ref-I expression and cellular localization in human thyroid carcinoma cell lines. J Endocrinol Invest. 2001;24(3):RC10–2.PubMed Russo D, Arturi F, Bulotta S, et al. ApeI/Ref-I expression and cellular localization in human thyroid carcinoma cell lines. J Endocrinol Invest. 2001;24(3):RC10–2.PubMed
16.
go back to reference Puglisi F, Barbone F, Tell G, et al. Prognostic role of Ape/Ref-1 subcellular expression in stage I-III breast carcinomas. Oncol Rep. 2002;9(1):11–7.PubMed Puglisi F, Barbone F, Tell G, et al. Prognostic role of Ape/Ref-1 subcellular expression in stage I-III breast carcinomas. Oncol Rep. 2002;9(1):11–7.PubMed
17.
go back to reference Zhang Y, Wang J, Xiang D, et al. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) in human ovarian cancer and indentification of the therapeutic potential of APE1/Ref-1 inhibitor. Int J Oncol. 2009;35(5):1069–79.PubMedCrossRef Zhang Y, Wang J, Xiang D, et al. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE1/Ref-1) in human ovarian cancer and indentification of the therapeutic potential of APE1/Ref-1 inhibitor. Int J Oncol. 2009;35(5):1069–79.PubMedCrossRef
18.
go back to reference Tell G, Fantini D, Quadrifoglio F. Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment. Cell Mol Life Sci. 2010;67(21):3589–608.PubMedCrossRef Tell G, Fantini D, Quadrifoglio F. Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment. Cell Mol Life Sci. 2010;67(21):3589–608.PubMedCrossRef
19.
go back to reference Abbotts R, Madhusudan S. Human AP endonuclease 1 (APE1): from mechanistic insights to druggable target in cancer. Cancer Treat Rev. 2010;36(5):425–35.PubMedCrossRef Abbotts R, Madhusudan S. Human AP endonuclease 1 (APE1): from mechanistic insights to druggable target in cancer. Cancer Treat Rev. 2010;36(5):425–35.PubMedCrossRef
20.
go back to reference Bisetto E, Domenis R, Comelli M, et al. New insights in the mitochondrial localization of APE1, the major apurinic/apyrimidinic endonuclease in mammals. Biochim Biophys Acta. 2010;179771–2. Bisetto E, Domenis R, Comelli M, et al. New insights in the mitochondrial localization of APE1, the major apurinic/apyrimidinic endonuclease in mammals. Biochim Biophys Acta. 2010;179771–2.
21.
go back to reference Tell G, Quadrifoglio F, Tiribelli C, et al. The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal. 2009;11(3):601–20.PubMedCrossRef Tell G, Quadrifoglio F, Tiribelli C, et al. The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal. 2009;11(3):601–20.PubMedCrossRef
22.
go back to reference Izumi T, Brown DB, Naidu CV, et al. Two essential but distinct functions of the mammalian abasic endonuclease. Proc Nat Acad Sci USA. 2005;102(16):5739–43.PubMedCrossRef Izumi T, Brown DB, Naidu CV, et al. Two essential but distinct functions of the mammalian abasic endonuclease. Proc Nat Acad Sci USA. 2005;102(16):5739–43.PubMedCrossRef
23.
go back to reference Yang S, Irani K, Chun S, et al. Expression of apurinic/apyrymidinic endonuclease/redox effector-1 (APE/Ref-1) is elevated with progression of human melanoma and the therapeutic potential of APE/Ref-1 inhibitors. Proc Am Assoc Cancer Res. 2005;2005(1):1043. Yang S, Irani K, Chun S, et al. Expression of apurinic/apyrymidinic endonuclease/redox effector-1 (APE/Ref-1) is elevated with progression of human melanoma and the therapeutic potential of APE/Ref-1 inhibitors. Proc Am Assoc Cancer Res. 2005;2005(1):1043.
24.
go back to reference Bobola MS, Emond MJ, Blank A, et al. Apurinic endonuclease activity in adult gliomas and time to tumor progression after alkylating agent-based chemotherapy and after radiotherapy. Clin Cancer Res. 2004;10(23):7875–83.PubMedCrossRef Bobola MS, Emond MJ, Blank A, et al. Apurinic endonuclease activity in adult gliomas and time to tumor progression after alkylating agent-based chemotherapy and after radiotherapy. Clin Cancer Res. 2004;10(23):7875–83.PubMedCrossRef
25.
go back to reference Daily D, Vlamis-Gardikas A, Offen D, et al. Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis by activating NF-kappa B via Ref-1. J Biol Chem. 2001;276(2):1335–44.PubMedCrossRef Daily D, Vlamis-Gardikas A, Offen D, et al. Glutaredoxin protects cerebellar granule neurons from dopamine-induced apoptosis by activating NF-kappa B via Ref-1. J Biol Chem. 2001;276(2):1335–44.PubMedCrossRef
26.
go back to reference Grösch S, Kaina B. Transcriptional activation of apurinic/apyrimidinic endonuclease (Ape, Ref-1) by oxidative stress requires CREB. Biochem Biophys Res Commun. 1999;261(3):859–63.PubMedCrossRef Grösch S, Kaina B. Transcriptional activation of apurinic/apyrimidinic endonuclease (Ape, Ref-1) by oxidative stress requires CREB. Biochem Biophys Res Commun. 1999;261(3):859–63.PubMedCrossRef
27.
go back to reference Kasahara T, Kuwayama C, Hashiba M, et al. The gene expression of hepatic proteins responsible for DNA repair and cell proliferation in tamoxifen-induced hepatocarcinogenesis. Cancer Sci. 2003;94(7):582–8.PubMedCrossRef Kasahara T, Kuwayama C, Hashiba M, et al. The gene expression of hepatic proteins responsible for DNA repair and cell proliferation in tamoxifen-induced hepatocarcinogenesis. Cancer Sci. 2003;94(7):582–8.PubMedCrossRef
28.
go back to reference Tell G, Crivellato E, Pines A, et al. Mitochondrial localization of APE/Ref-1 in thyroid cells. Mutat Res. 2001;485(2):143–52.PubMed Tell G, Crivellato E, Pines A, et al. Mitochondrial localization of APE/Ref-1 in thyroid cells. Mutat Res. 2001;485(2):143–52.PubMed
29.
go back to reference Fung H, Kow YW, Van Houten B, et al. Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. Cancer Res. 1998;58(2):189–94.PubMed Fung H, Kow YW, Van Houten B, et al. Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. Cancer Res. 1998;58(2):189–94.PubMed
30.
go back to reference Fan Z, Beresford PJ, Zhang D, et al. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003;4(2):145–53.PubMedCrossRef Fan Z, Beresford PJ, Zhang D, et al. Cleaving the oxidative repair protein Ape1 enhances cell death mediated by granzyme A. Nat Immunol. 2003;4(2):145–53.PubMedCrossRef
31.
go back to reference Fan Z, Beresford PJ, Zhang D, et al. HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Mol Cell Biol. 2002;22(8):2810–20.PubMedCrossRef Fan Z, Beresford PJ, Zhang D, et al. HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A. Mol Cell Biol. 2002;22(8):2810–20.PubMedCrossRef
32.
go back to reference Duguid JR, Eble JN, Wilson TM, et al. Differential cellular and subcellular expression of the human multifunctional apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme. Cancer Res. 1995;55(24):6097–102.PubMed Duguid JR, Eble JN, Wilson TM, et al. Differential cellular and subcellular expression of the human multifunctional apurinic/apyrimidinic endonuclease (APE/ref-1) DNA repair enzyme. Cancer Res. 1995;55(24):6097–102.PubMed
33.
go back to reference Barnes T, Kim WC, Mantha AK, et al. Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA. Nucleic Acids Res. 2009;37(12):3946–58.PubMedCrossRef Barnes T, Kim WC, Mantha AK, et al. Identification of Apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA. Nucleic Acids Res. 2009;37(12):3946–58.PubMedCrossRef
34.
go back to reference Vascotto C, Fantini D, Romanello M, et al. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol. 2009;29(7):1834–54.PubMedCrossRef Vascotto C, Fantini D, Romanello M, et al. APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol. 2009;29(7):1834–54.PubMedCrossRef
35.
go back to reference Tell G, Wilson DM 3rd, Lee CH. Intrusion of a DNA repair protein in the RNome world: is this the beginning of a new era? Mol Cell Biol. 2010;30(2):366–71.PubMedCrossRef Tell G, Wilson DM 3rd, Lee CH. Intrusion of a DNA repair protein in the RNome world: is this the beginning of a new era? Mol Cell Biol. 2010;30(2):366–71.PubMedCrossRef
Metadata
Title
Prognostic significance of APE1 cytoplasmic localization in human epithelial ovarian cancer
Authors
Qingsong Sheng
Ying Zhang
Rui Wang
Jianfang Zhang
Biliang Chen
Jian Wang
Wei Zhang
Xiaoyan Xin
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9931-y

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