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Published in: Journal of Ovarian Research 1/2014

Open Access 01-12-2014 | Research

The level of RECQL1 expression is a prognostic factor for epithelial ovarian cancer

Authors: Yoko Matsushita, Yoshihito Yokoyama, Hidemi Yoshida, Yuki Osawa, Makito Mizunuma, Tatsuhiko Shigeto, Masayuki Futagami, Tadaastu Imaizumi, Hideki Mizunuma

Published in: Journal of Ovarian Research | Issue 1/2014

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Abstract

Background

The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.

Methods

The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(−) cells).

Results

The level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P = 0.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(−) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(−) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(−) cells than in RECQL1(+) cells.

Conclusions

These results suggest that RECQL1 is a prognostic factor for EOC and that RECQL1 contributes to potential malignancy by inhibiting apoptosis.
Appendix
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Literature
1.
go back to reference Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013,63(1):11–30. 10.3322/caac.21166CrossRefPubMed Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin 2013,63(1):11–30. 10.3322/caac.21166CrossRefPubMed
2.
go back to reference Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U: Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 2006, 95: S161-S192. 10.1016/S0020-7292(06)60033-7CrossRefPubMed Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U: Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 2006, 95: S161-S192. 10.1016/S0020-7292(06)60033-7CrossRefPubMed
3.
go back to reference Yokoyama Y, Futagami M, Watanabe J, Sato N, Terada Y, Miura F, Sugiyama T, Takano T, Yaegashi N, Kojimahara T, Kurachi H, Nishiyama H, Fujimori K, Tase T, Mizunuma H: Redistribution of resistance and sensitivity to platinum during the observation period following treatment of epithelial ovarian cancer. Mol Clin Oncol 2014,2(2):212–218.PubMedCentralPubMed Yokoyama Y, Futagami M, Watanabe J, Sato N, Terada Y, Miura F, Sugiyama T, Takano T, Yaegashi N, Kojimahara T, Kurachi H, Nishiyama H, Fujimori K, Tase T, Mizunuma H: Redistribution of resistance and sensitivity to platinum during the observation period following treatment of epithelial ovarian cancer. Mol Clin Oncol 2014,2(2):212–218.PubMedCentralPubMed
4.
go back to reference Nakayama H, Nakayama K, Nakayama R, Irino N, Nakayama Y, Hanawalt PC: Isolation and genetic characterization of a thymineless death-resistant mutant of Escherichia coli K12: identification of a new mutation (recQ1) that blocks the RecF recombination pathway. Mol Gen Genet 1984,195(3):474–480. 10.1007/BF00341449CrossRefPubMed Nakayama H, Nakayama K, Nakayama R, Irino N, Nakayama Y, Hanawalt PC: Isolation and genetic characterization of a thymineless death-resistant mutant of Escherichia coli K12: identification of a new mutation (recQ1) that blocks the RecF recombination pathway. Mol Gen Genet 1984,195(3):474–480. 10.1007/BF00341449CrossRefPubMed
5.
go back to reference Sinclair DA, Guarente L: Extrachromosomal rDNA circles–a cause of aging in yeast. Cell 1997,91(7):1033–1042. 10.1016/S0092-8674(00)80493-6CrossRefPubMed Sinclair DA, Guarente L: Extrachromosomal rDNA circles–a cause of aging in yeast. Cell 1997,91(7):1033–1042. 10.1016/S0092-8674(00)80493-6CrossRefPubMed
6.
go back to reference Furuichi Y: Premature aging and predisposition to cancers caused by mutations in RecQ family helicases. Ann N Y Acad Sci 2001, 928: 121–131. 10.1111/j.1749-6632.2001.tb05642.xCrossRefPubMed Furuichi Y: Premature aging and predisposition to cancers caused by mutations in RecQ family helicases. Ann N Y Acad Sci 2001, 928: 121–131. 10.1111/j.1749-6632.2001.tb05642.xCrossRefPubMed
7.
go back to reference Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y: Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet 1999,22(1):82–84. 10.1038/8788CrossRefPubMed Kitao S, Shimamoto A, Goto M, Miller RW, Smithson WA, Lindor NM, Furuichi Y: Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet 1999,22(1):82–84. 10.1038/8788CrossRefPubMed
8.
go back to reference Hickson ID, Davies SL, Li JL, Levitt NC, Mohaghegh P, North PS, Wu L: Role of the Bloom's syndrome helicase in maintenance of genome stability. Biochem Soc Trans 2001, 29: 201–204. 10.1042/BST0290201CrossRefPubMed Hickson ID, Davies SL, Li JL, Levitt NC, Mohaghegh P, North PS, Wu L: Role of the Bloom's syndrome helicase in maintenance of genome stability. Biochem Soc Trans 2001, 29: 201–204. 10.1042/BST0290201CrossRefPubMed
9.
go back to reference Watt PM, Hickson ID, Borts RH, Louis EJ: SGS1, a homologue of the Bloom’s and Werner’s syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics 1996,144(3):935–945.PubMedCentralPubMed Watt PM, Hickson ID, Borts RH, Louis EJ: SGS1, a homologue of the Bloom’s and Werner’s syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics 1996,144(3):935–945.PubMedCentralPubMed
10.
go back to reference Seki M, Miyazawa H, Tada S, Yanagisawa J, Yamaoka T, Hoshino S, Ozawa K, Eki T, Nogami M, Okumura K, Taguchi H, Hanaoka F, Enomoto T: Molecular cloning of cDNA encoding human DNA helicase Q1 which has homology to Escherichia coli Rec Q helicase and localization of the gene at chromosome 12p12. Nucleic Acids Res 1994,22(22):4566–4573. 10.1093/nar/22.22.4566PubMedCentralCrossRefPubMed Seki M, Miyazawa H, Tada S, Yanagisawa J, Yamaoka T, Hoshino S, Ozawa K, Eki T, Nogami M, Okumura K, Taguchi H, Hanaoka F, Enomoto T: Molecular cloning of cDNA encoding human DNA helicase Q1 which has homology to Escherichia coli Rec Q helicase and localization of the gene at chromosome 12p12. Nucleic Acids Res 1994,22(22):4566–4573. 10.1093/nar/22.22.4566PubMedCentralCrossRefPubMed
11.
go back to reference Thangavel S, Mendoza-Maldonado R, Tissino E, Sidorova JM, Yin J, Wang W, Monnat RJ Jr, Falaschi A, Vindigni A: Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol Cell Biol 2010,30(6):1382–1396. 10.1128/MCB.01290-09PubMedCentralCrossRefPubMed Thangavel S, Mendoza-Maldonado R, Tissino E, Sidorova JM, Yin J, Wang W, Monnat RJ Jr, Falaschi A, Vindigni A: Human RECQ1 and RECQ4 helicases play distinct roles in DNA replication initiation. Mol Cell Biol 2010,30(6):1382–1396. 10.1128/MCB.01290-09PubMedCentralCrossRefPubMed
12.
go back to reference Futami K, Kumagai E, Makino H, Sato A, Takagi M, Shimamoto A, Furuichi Y: Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models. Cancer Sci 2008,99(6):1227–1236. 10.1111/j.1349-7006.2008.00794.xCrossRefPubMed Futami K, Kumagai E, Makino H, Sato A, Takagi M, Shimamoto A, Furuichi Y: Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models. Cancer Sci 2008,99(6):1227–1236. 10.1111/j.1349-7006.2008.00794.xCrossRefPubMed
13.
go back to reference Futami K, Ogasawara S, Goto H, Yano H, Furuichi Y: RecQL1 DNA repair helicase: a potential tumor marker and therapeutic target against hepatocellular carcinoma. Int J Mol Med 2010,25(4):537–545.PubMed Futami K, Ogasawara S, Goto H, Yano H, Furuichi Y: RecQL1 DNA repair helicase: a potential tumor marker and therapeutic target against hepatocellular carcinoma. Int J Mol Med 2010,25(4):537–545.PubMed
14.
go back to reference Arai A, Chano T, Futami K, Furuichi Y, Ikebuchi K, Inui T, Tameno H, Ochi Y, Shimada T, Hisa Y, Okabe H: RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma. Cancer Res 2011,71(13):4598–4607. 10.1158/0008-5472.CAN-11-0320CrossRefPubMed Arai A, Chano T, Futami K, Furuichi Y, Ikebuchi K, Inui T, Tameno H, Ochi Y, Shimada T, Hisa Y, Okabe H: RECQL1 and WRN proteins are potential therapeutic targets in head and neck squamous cell carcinoma. Cancer Res 2011,71(13):4598–4607. 10.1158/0008-5472.CAN-11-0320CrossRefPubMed
15.
go back to reference Sanada S, Futami K, Terada A, Yonemoto K, Ogasawara S, Akiba J, Yasumoto M, Sumi A, Ushijima K, Kamura T, Furuichi Y, Yano H: RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer. PLoS One 2013,8(8):e72820. 10.1371/journal.pone.0072820PubMedCentralCrossRefPubMed Sanada S, Futami K, Terada A, Yonemoto K, Ogasawara S, Akiba J, Yasumoto M, Sumi A, Ushijima K, Kamura T, Furuichi Y, Yano H: RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer. PLoS One 2013,8(8):e72820. 10.1371/journal.pone.0072820PubMedCentralCrossRefPubMed
16.
go back to reference Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K, Itoh K, Takahashi I, Imaizumi T: Carnosic acid suppresses the production of amyloid-β 1–42 and 1–43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells. Neurosci Res 2014, 79: 83–93. 10.1016/j.neures.2013.11.004CrossRefPubMed Yoshida H, Meng P, Matsumiya T, Tanji K, Hayakari R, Xing F, Wang L, Tsuruga K, Tanaka H, Mimura J, Kosaka K, Itoh K, Takahashi I, Imaizumi T: Carnosic acid suppresses the production of amyloid-β 1–42 and 1–43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells. Neurosci Res 2014, 79: 83–93. 10.1016/j.neures.2013.11.004CrossRefPubMed
17.
go back to reference Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C: Clonogenic assay of cells in vitro. Nat Protoc 2006,1(5):2315–2319. 10.1038/nprot.2006.339CrossRefPubMed Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C: Clonogenic assay of cells in vitro. Nat Protoc 2006,1(5):2315–2319. 10.1038/nprot.2006.339CrossRefPubMed
18.
go back to reference Kawabe T, Tsuyama N, Kitao S, Nishikawa K, Shimamoto A, Shiratori M, Matsumoto T, Anno K, Sato T, Mitsui Y, Seki M, Enomoto T, Goto M, Ellis NA, Ide T, Furuichi Y, Sugimoto M: Differential regulation of human RecQ family helicases in cell transformation and cell cycle. Oncogene 2000,19(41):4764–4772. 10.1038/sj.onc.1203841CrossRefPubMed Kawabe T, Tsuyama N, Kitao S, Nishikawa K, Shimamoto A, Shiratori M, Matsumoto T, Anno K, Sato T, Mitsui Y, Seki M, Enomoto T, Goto M, Ellis NA, Ide T, Furuichi Y, Sugimoto M: Differential regulation of human RecQ family helicases in cell transformation and cell cycle. Oncogene 2000,19(41):4764–4772. 10.1038/sj.onc.1203841CrossRefPubMed
19.
go back to reference Zhang P, Zhang Z, Zhou X, Qiu W, Chen F, Chen W: Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line. BMC Cancer 2006, 6: 224. 10.1186/1471-2407-6-224PubMedCentralCrossRefPubMed Zhang P, Zhang Z, Zhou X, Qiu W, Chen F, Chen W: Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line. BMC Cancer 2006, 6: 224. 10.1186/1471-2407-6-224PubMedCentralCrossRefPubMed
20.
go back to reference Mimnaugh EG, Yunmbam MK, Li Q, Bonvini P, Hwang SG, Trepel J, Reed E, Neckers L: Prevention of cisplatin-DNA adduct repair and potentiation of cisplatin-induced apoptosis in ovarian carcinoma cells by proteasome inhibitors. Biochem Pharmacol 2000,60(9):1343–1354. 10.1016/S0006-2952(00)00455-XCrossRefPubMed Mimnaugh EG, Yunmbam MK, Li Q, Bonvini P, Hwang SG, Trepel J, Reed E, Neckers L: Prevention of cisplatin-DNA adduct repair and potentiation of cisplatin-induced apoptosis in ovarian carcinoma cells by proteasome inhibitors. Biochem Pharmacol 2000,60(9):1343–1354. 10.1016/S0006-2952(00)00455-XCrossRefPubMed
21.
go back to reference Nyberg KA, Michelson RJ, Putnam CW, Weinert TA: Toward maintaining the genome: DNA damage and replication checkpoints. Annu Rev Genet 2002, 36: 617–656. 10.1146/annurev.genet.36.060402.113540CrossRefPubMed Nyberg KA, Michelson RJ, Putnam CW, Weinert TA: Toward maintaining the genome: DNA damage and replication checkpoints. Annu Rev Genet 2002, 36: 617–656. 10.1146/annurev.genet.36.060402.113540CrossRefPubMed
22.
go back to reference Ngan CY, Yamamoto H, Takagi A, Fujie Y, Takemasa I, Ikeda M, Takahashi-Yanaga F, Sasaguri T, Sekimoto M, Matsuura N, Monden M: Oxaliplatin induces mitotic catastrophe and apoptosis in esophageal cancer cells. Cancer Sci 2008,99(1):129–139.PubMed Ngan CY, Yamamoto H, Takagi A, Fujie Y, Takemasa I, Ikeda M, Takahashi-Yanaga F, Sasaguri T, Sekimoto M, Matsuura N, Monden M: Oxaliplatin induces mitotic catastrophe and apoptosis in esophageal cancer cells. Cancer Sci 2008,99(1):129–139.PubMed
23.
go back to reference de Bruin EC, Medema JP: Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev 2008,34(8):737–749. 10.1016/j.ctrv.2008.07.001CrossRefPubMed de Bruin EC, Medema JP: Apoptosis and non-apoptotic deaths in cancer development and treatment response. Cancer Treat Rev 2008,34(8):737–749. 10.1016/j.ctrv.2008.07.001CrossRefPubMed
24.
go back to reference Tao J, Tao S, Han J, Zhou Z, Zhang X, Wang H, Chen R, Ji F, Zhu Y: RECQL1 plays an important role in the development of tongue squamous cell carcinoma. Cell Physiol Biochem 2014,33(5):1579–1590. 10.1159/000358721CrossRefPubMed Tao J, Tao S, Han J, Zhou Z, Zhang X, Wang H, Chen R, Ji F, Zhu Y: RECQL1 plays an important role in the development of tongue squamous cell carcinoma. Cell Physiol Biochem 2014,33(5):1579–1590. 10.1159/000358721CrossRefPubMed
Metadata
Title
The level of RECQL1 expression is a prognostic factor for epithelial ovarian cancer
Authors
Yoko Matsushita
Yoshihito Yokoyama
Hidemi Yoshida
Yuki Osawa
Makito Mizunuma
Tatsuhiko Shigeto
Masayuki Futagami
Tadaastu Imaizumi
Hideki Mizunuma
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2014
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-014-0107-1

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