Relationship of Topoisomerase TypeⅡA to Anthracycline in Breast Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YANGYan-hua ,  WANGShu-sen

Cancer Center of Sun Yat-sen University/State Key Laboratory of Oncology in South China, Guangzhou 510060, Guangdong Province, China;

Corresponding author：

WANGShu-sen, Email: wangshs@sysucc.org.cn

Keywords：

Breast cancer; Topoisomerase typeⅡA gene; Anthracycline; Curative effect

DOI：

10.7507/1007-9424.20140247

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To explore the relationship of topoisomerase typeⅡA (TOP2A)to human epidermal growth factor receptor 2(HER2/neu), and the therapeutic prediction of TOP2A in clinical chemotherapy for breast cancer. Method The Cochrane, Medline, Embase, PubMed, CNKI, and WANFANG data were retrieved to get the related literatures about TOP2A and the effect of anthracycline-based drugs. Results The TOP2A gene and HER2 gene were all located in 17q21, the TOP2A gene was a downstream gene of the HER2 gene. There was some relationship of the HER2 to TOP2A gene abnormality. There was some controversy about HER2 and TOP2A on anthracycline regimens reaction. It was generally accepted that the status of TOP2A gene for predicting the effect of patients with anthracycline regimens might be more precise. There was inconsistency between the gene amplification and overexpression of TOP2A, which was two different biological behaviors, and which might be the characteristics of different molecular subtypes. In terms of the present study, a plenty of clinical researches could illustrate that TOP2A was an important target of anthracycline. But anthracycline-based drugs could induce the apoptosis of the cell through various mechanisms, so the anthracyclinebased drugs killed tumor cells in breast cancer needed not inhibit TOP2A, might be more complex than previously predicted. Conclusions TOP2A is an important target of anthracycline. But it seems to be limited only by observing the TOP2A for predicting curative effect of anthracycline-based drugs.

Citation： YANGYan-hua, WANGShu-sen. Relationship of Topoisomerase TypeⅡA to Anthracycline in Breast Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(8): 1029-1033. doi: 10.7507/1007-9424.20140247 Copy

1.	Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009[J]. CA Cancer J Clin, 2009, 59(4):225-249.
2.	Wang JC. Cellular roles of DNA topoisomerases:a molecular perspective[J]. Nat Rev Mol Cell Biol, 2002, 3(6):430-440.
3.	Collins TR, Hammes GG, Hsieh TS. Analysis of the eukaryotic topoisomeraseⅡDNA gate:a single-molecule FRET and structural perspective[J]. Nucleic Acids Res, 2009, 37(3):712-720.
4.	Osheroff N, Zechiedrich EL, Gale KC. Catalytic function of DNA topoisomeraseⅡ[J]. Bioessays, 1991, 13(6):269-273.
5.	Earnshaw WC, Halligan B, Cooke CA, et al. TopoisomeraseⅡis a structural component of mitotic chromosome scaffolds[J]. J Cell Biol, 1985, 100(5):1706-1715.
6.	Drake FH, Hofmann GA, Bartus HF, et al. Biochemical and pharmacological properties of p170 and p180 forms of topoisom-eraseⅡ[J]. Biochemistry, 1989, 28(20):8154-8160.
7.	Goswami PC, Sheren J, Albee LD, et al. Cell cycle-coupled variation in topoisomeraseⅡalpha mRNA is regulated by the 3'-untranslated region. Possible role of redox-sensitive protein binding in mRNA accumulation[J]. J Biol Chem, 2000, 275(49):38384-38392.
8.	Christensen MO, Larsen MK, Barthelmes HU, et al. Dynamics of human DNA topoisomerasesⅡalpha andⅡbeta in living cells[J]. J Cell Biol, 2002, 157(1):31-44.
9.	Isaacs RJ, Harris AL, Hickson ID. Regulation of the human topoisomeraseⅡalpha gene promoter in confluence-arrested cells[J]. J Biol Chem, 1996, 271(28):16741-16747.
10.	Goswami PC, Roti Roti JL, Hunt CR. The cell cycle-coupled expression of topoisomeraseⅡalpha during S phase is regulated by mRNA stability and is disrupted by heat shock or ionizing radiation[J]. Mol Cell Biol, 1996, 16(4):1500-1508.
11.	Simůnek T, Stérba M, Popelová O, et al. Anthracycline-induced cardiotoxicity:overview of studies examining the roles of oxidative stress and free cellular iron[J]. Pharmacol Rep, 2009, 61(1):154-171.
12.	韩锐, 孙燕.新世纪癌的化学预防与药物治疗[M].北京:人民军医出版社, 2005:108.
13.	Hussein MR, Abd-Elwahed SR, Abdulwahed AR. Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast[J]. Cell Biol Int, 2008, 32(6):698-707.
14.	Lehr HA, Schaefer SC, Delaloye JF. Predictive value of Her2/neu expression/amplification for the targeted treatment of breast cancer[J]. Rev Med Suisse, 2009, 5(211):1525-1529.
15.	Burden DA, Osheroff N. Mechanism of action of eukaryotic topoisomeraseⅡand drugs targeted to the enzyme[J]. Biochim Biophys Acta, 1998, 1400(1-3):139-154.
16.	Chen H, Pimienta G, Gu Y, et al. Proteomic characterization of Her2/neu-overexpressing breast cancer cells[J]. Proteomics, 2010, 10(21):3800-3810.
17.	Sivridis E, Stamos C, Fiska A, et al. c-erbB-2 and the "triplestate" in early breast carcinomas[J]. Med Oncol, 2010, 27(3): 578-584.
18.	Chen XS, Ma CD, Wu JY, et al. Molecular subtype approximated by quantitative estrogen receptor, progesterone receptor and Her2 can predict the prognosis of breast cancer[J]. Tumori, 2010, 96(1):103-110.
19.	Olsen KE, Knudsen H, Rasmussen BB, et al. Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes[J]. Acta Oncol, 2004, 43(1): 35-42.
20.	Järvinen TA1, Tanner M, Bärlund M, et al. Characterization of topoisomeraseⅡalpha gene amplification and deletion in breast cancer[J]. Genes Chromosomes Cancer, 1999, 26(2):142-150.
21.	Bouchalova K, Cizkova M, Cwiertka K, et al. Triple negative breast cancer-current status and prospective targeted treatment based on HER1(EGFR), TOP2A and C-MYC gene assessment[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2009, 153(1):13-17.
22.	Thor AD, Berry DA, Budman DR, et al. erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer[J]. J Natl Cancer Inst, 1998, 90(18):1346-1360.
23.	Paik S, Bryant J, Park C, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer[J]. J Natl Cancer Inst, 1998, 90(18):1361-1370.
24.	Paik S, Bryant J, Tan-Chiu E, et al. HER2 and choice of adjuvant chemotherapy for invasive breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-15[J]. J Natl Cancer Inst, 2000, 92(24):1991-1998.
25.	Pritchard KI, Shepherd LE, O'Malley FP, et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy[J]. N Engl J Med, 2006, 354(20):2103-2111.
26.	Bartlett JM, Munro A, Cameron DA, et al. Type 1 receptor tyrosine kinase profiles identify patients with enhanced benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial[J]. J Clin Oncol, 2008, 26(31):5027-5035.
27.	Press MF, Sauter G, Buyse M, et al. Alteration of topoisomeraseⅡ-alpha gene in human breast cancer:association with responsiveness to anthracycline-based chemotherapy[J]. J Clin Oncol, 2011, 29(7):859-867.
28.	Knoop AS, Knudsen H, Balslev E, et al. Retrospective analysis of topoisomeraseⅡαamplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil:Danish Breast Cancer Cooperative Group[J]. J Clin Oncol, 2005, 23(30):7483-7490.
29.	Romero A, Martín M, Cheang MC, et al. Assessment of TopoisomeraseⅡαstatus in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization[J]. Am J Pathol, 2011, 178(4):1453-1460.
30.	Di Leo A, Desmedt C, Bartlett JM, et al. HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer:a meta-analysis of individual patient data[J]. Lancet Oncol, 2011, 12(12): 1134-1142.
31.	O'Malley FP, Chia S, Tu D, et al. TopoisomeraseⅡalpha and responsiveness of breast cancer to adjuvant chemotherapy[J]. J Natl Cancer Inst, 2009, 101(9):644-650.
32.	Harris LN, Broadwater G, Abu-Khalaf M, et al. TopoisomeraseⅡαamplification does not predict benefit from dose-intense cyclophosphamide, doxorubicin, and fluorouracil therapy in HER2-amplified early breast cancer:results of CALGB 8541/150013[J]. J Clin Oncol, 2009, 27(21):3430-3436.
33.	Hannemann J, Kristel P, van Tinteren H, et al. Molecular subtypes of breast cancer and amplification of topoisomeraseⅡalpha: predictive role in dose intensive adjuvant chemotherapy[J]. Br J Cancer, 2006, 95(10):1334-1341.
34.	Bartlett JM, Munro AF, Dunn JA, et al. Predictive markers of anthracycline benefit:a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601)[J]. Lancet Oncol, 2010, 11(3):266-274.
35.	Gudkov AV, Zelnick CR, Kazarov AR, et al. Isolation of genetic suppressor elements, inducing resistance to topoisomeraseⅡ-interactive cytotoxic drugs, from human topoisomeraseⅡcDNA[J]. Proc Natl Acad Sci U S A, 1993, 90(8):3231-3235.
36.	Mo YY, Ameiss KA, Beck WT. Overexpression of human DNA topoisomeraseⅡalpha by fusion to enhanced green fluorescent protein[J]. Biotechniques, 1998, 25(6):1052-1057.
37.	Weiss RB. The anthracyclines:will we ever find a better doxorubicin?[J]. Semin Oncol, 1992, 19(6):670-686.
38.	Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer:an overview of the randomised trials[J]. Lancet, 1998, 352(9132):930-942.
39.	Deo SV, Bhutani M, Shukla NK, et al. Randomized trial comparing neo-adjuvant versus adjuvant chemotherapy in operable locally advanced breast cancer (T4b N0-2 M0)[J]. J Surg Oncol, 2003, 84(4):192-197.
40.	Bonneterre J, Dieras V, Tubiana-Hulin M, et al. PhaseⅡmulticentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer[J]. Br J Cancer, 2004, 91(8):1466-1471.
41.	Ho E, Brown A, Barrett P, et al. Subclinical anthracycline-and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors:a speckle tracking echocardiographic study[J]. Heart, 2010, 96(9):701-707.
42.	Hrdina R, Gersl V, Klimtová I, et al. Anthracycline-induced cardiotoxicity[J]. Acta Medica (Hradec Kralove), 2000, 43(3): 75-82.

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009[J]. CA Cancer J Clin, 2009, 59(4):225-249.
2. Wang JC. Cellular roles of DNA topoisomerases:a molecular perspective[J]. Nat Rev Mol Cell Biol, 2002, 3(6):430-440.
3. Collins TR, Hammes GG, Hsieh TS. Analysis of the eukaryotic topoisomeraseⅡDNA gate:a single-molecule FRET and structural perspective[J]. Nucleic Acids Res, 2009, 37(3):712-720.
4. Osheroff N, Zechiedrich EL, Gale KC. Catalytic function of DNA topoisomeraseⅡ[J]. Bioessays, 1991, 13(6):269-273.
5. Earnshaw WC, Halligan B, Cooke CA, et al. TopoisomeraseⅡis a structural component of mitotic chromosome scaffolds[J]. J Cell Biol, 1985, 100(5):1706-1715.
6. Drake FH, Hofmann GA, Bartus HF, et al. Biochemical and pharmacological properties of p170 and p180 forms of topoisom-eraseⅡ[J]. Biochemistry, 1989, 28(20):8154-8160.
7. Goswami PC, Sheren J, Albee LD, et al. Cell cycle-coupled variation in topoisomeraseⅡalpha mRNA is regulated by the 3'-untranslated region. Possible role of redox-sensitive protein binding in mRNA accumulation[J]. J Biol Chem, 2000, 275(49):38384-38392.
8. Christensen MO, Larsen MK, Barthelmes HU, et al. Dynamics of human DNA topoisomerasesⅡalpha andⅡbeta in living cells[J]. J Cell Biol, 2002, 157(1):31-44.
9. Isaacs RJ, Harris AL, Hickson ID. Regulation of the human topoisomeraseⅡalpha gene promoter in confluence-arrested cells[J]. J Biol Chem, 1996, 271(28):16741-16747.
10. Goswami PC, Roti Roti JL, Hunt CR. The cell cycle-coupled expression of topoisomeraseⅡalpha during S phase is regulated by mRNA stability and is disrupted by heat shock or ionizing radiation[J]. Mol Cell Biol, 1996, 16(4):1500-1508.
11. Simůnek T, Stérba M, Popelová O, et al. Anthracycline-induced cardiotoxicity:overview of studies examining the roles of oxidative stress and free cellular iron[J]. Pharmacol Rep, 2009, 61(1):154-171.
12. 韩锐, 孙燕.新世纪癌的化学预防与药物治疗[M].北京:人民军医出版社, 2005:108.
13. Hussein MR, Abd-Elwahed SR, Abdulwahed AR. Alterations of estrogen receptors, progesterone receptors and c-erbB2 oncogene protein expression in ductal carcinomas of the breast[J]. Cell Biol Int, 2008, 32(6):698-707.
14. Lehr HA, Schaefer SC, Delaloye JF. Predictive value of Her2/neu expression/amplification for the targeted treatment of breast cancer[J]. Rev Med Suisse, 2009, 5(211):1525-1529.
15. Burden DA, Osheroff N. Mechanism of action of eukaryotic topoisomeraseⅡand drugs targeted to the enzyme[J]. Biochim Biophys Acta, 1998, 1400(1-3):139-154.
16. Chen H, Pimienta G, Gu Y, et al. Proteomic characterization of Her2/neu-overexpressing breast cancer cells[J]. Proteomics, 2010, 10(21):3800-3810.
17. Sivridis E, Stamos C, Fiska A, et al. c-erbB-2 and the "triplestate" in early breast carcinomas[J]. Med Oncol, 2010, 27(3): 578-584.
18. Chen XS, Ma CD, Wu JY, et al. Molecular subtype approximated by quantitative estrogen receptor, progesterone receptor and Her2 can predict the prognosis of breast cancer[J]. Tumori, 2010, 96(1):103-110.
19. Olsen KE, Knudsen H, Rasmussen BB, et al. Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes[J]. Acta Oncol, 2004, 43(1): 35-42.
20. Järvinen TA1, Tanner M, Bärlund M, et al. Characterization of topoisomeraseⅡalpha gene amplification and deletion in breast cancer[J]. Genes Chromosomes Cancer, 1999, 26(2):142-150.
21. Bouchalova K, Cizkova M, Cwiertka K, et al. Triple negative breast cancer-current status and prospective targeted treatment based on HER1(EGFR), TOP2A and C-MYC gene assessment[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2009, 153(1):13-17.
22. Thor AD, Berry DA, Budman DR, et al. erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer[J]. J Natl Cancer Inst, 1998, 90(18):1346-1360.
23. Paik S, Bryant J, Park C, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer[J]. J Natl Cancer Inst, 1998, 90(18):1361-1370.
24. Paik S, Bryant J, Tan-Chiu E, et al. HER2 and choice of adjuvant chemotherapy for invasive breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-15[J]. J Natl Cancer Inst, 2000, 92(24):1991-1998.
25. Pritchard KI, Shepherd LE, O'Malley FP, et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy[J]. N Engl J Med, 2006, 354(20):2103-2111.
26. Bartlett JM, Munro A, Cameron DA, et al. Type 1 receptor tyrosine kinase profiles identify patients with enhanced benefit from anthracyclines in the BR9601 adjuvant breast cancer chemotherapy trial[J]. J Clin Oncol, 2008, 26(31):5027-5035.
27. Press MF, Sauter G, Buyse M, et al. Alteration of topoisomeraseⅡ-alpha gene in human breast cancer:association with responsiveness to anthracycline-based chemotherapy[J]. J Clin Oncol, 2011, 29(7):859-867.
28. Knoop AS, Knudsen H, Balslev E, et al. Retrospective analysis of topoisomeraseⅡαamplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil:Danish Breast Cancer Cooperative Group[J]. J Clin Oncol, 2005, 23(30):7483-7490.
29. Romero A, Martín M, Cheang MC, et al. Assessment of TopoisomeraseⅡαstatus in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization[J]. Am J Pathol, 2011, 178(4):1453-1460.
30. Di Leo A, Desmedt C, Bartlett JM, et al. HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer:a meta-analysis of individual patient data[J]. Lancet Oncol, 2011, 12(12): 1134-1142.
31. O'Malley FP, Chia S, Tu D, et al. TopoisomeraseⅡalpha and responsiveness of breast cancer to adjuvant chemotherapy[J]. J Natl Cancer Inst, 2009, 101(9):644-650.
32. Harris LN, Broadwater G, Abu-Khalaf M, et al. TopoisomeraseⅡαamplification does not predict benefit from dose-intense cyclophosphamide, doxorubicin, and fluorouracil therapy in HER2-amplified early breast cancer:results of CALGB 8541/150013[J]. J Clin Oncol, 2009, 27(21):3430-3436.
33. Hannemann J, Kristel P, van Tinteren H, et al. Molecular subtypes of breast cancer and amplification of topoisomeraseⅡalpha: predictive role in dose intensive adjuvant chemotherapy[J]. Br J Cancer, 2006, 95(10):1334-1341.
34. Bartlett JM, Munro AF, Dunn JA, et al. Predictive markers of anthracycline benefit:a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601)[J]. Lancet Oncol, 2010, 11(3):266-274.
35. Gudkov AV, Zelnick CR, Kazarov AR, et al. Isolation of genetic suppressor elements, inducing resistance to topoisomeraseⅡ-interactive cytotoxic drugs, from human topoisomeraseⅡcDNA[J]. Proc Natl Acad Sci U S A, 1993, 90(8):3231-3235.
36. Mo YY, Ameiss KA, Beck WT. Overexpression of human DNA topoisomeraseⅡalpha by fusion to enhanced green fluorescent protein[J]. Biotechniques, 1998, 25(6):1052-1057.
37. Weiss RB. The anthracyclines:will we ever find a better doxorubicin?[J]. Semin Oncol, 1992, 19(6):670-686.
38. Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer:an overview of the randomised trials[J]. Lancet, 1998, 352(9132):930-942.
39. Deo SV, Bhutani M, Shukla NK, et al. Randomized trial comparing neo-adjuvant versus adjuvant chemotherapy in operable locally advanced breast cancer (T4b N0-2 M0)[J]. J Surg Oncol, 2003, 84(4):192-197.
40. Bonneterre J, Dieras V, Tubiana-Hulin M, et al. PhaseⅡmulticentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer[J]. Br J Cancer, 2004, 91(8):1466-1471.
41. Ho E, Brown A, Barrett P, et al. Subclinical anthracycline-and trastuzumab-induced cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors:a speckle tracking echocardiographic study[J]. Heart, 2010, 96(9):701-707.
42. Hrdina R, Gersl V, Klimtová I, et al. Anthracycline-induced cardiotoxicity[J]. Acta Medica (Hradec Kralove), 2000, 43(3): 75-82.

Previous Article
Research Progress of Myeloid Derived Suppressor Cells and Pancreatic Cancer
Next Article
Research Progress in Application and Complications of Pancreaticogastrostomy

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relationship of Topoisomerase TypeⅡA to Anthracycline in Breast Cancer

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content