Skip to main content

Advertisement

SpringerLink
Log in

Establishment and characterization of a novel ovarian clear cell carcinoma cell line, TU-OC-2, with loss of ARID1A expression

  • Cell Line
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

A new cell line of human ovarian clear cell carcinoma (CCC), TU-OC-2, was established and characterized. The cells were polygonal in shape, grew in monolayers without contact inhibition and were arranged in islands like pieces of a jigsaw puzzle. The chromosome numbers ranged from 41 to 96. A low rate of proliferation was observed and the doubling time was 37.5 h. The IC50 values of cisplatin, 7-ethyl-10-hydroxycamptothecin (SN38), which is an active metabolite of camptothecin, and paclitaxel were 7.7 μM, 17.7 nM and 301 nM, respectively. The drug sensitivity assay indicated that TU-OC-2 was sensitive to SN38, but resistant to cisplatin and paclitaxel. Mutational analysis revealed that TU-OC-2 cells have no mutations of PIK3CA in exons 9 and 20 and of TP53 in exons 4–9. We observed the loss of ARID1A protein expression in TU-OC-2 cells by western blot analysis and in the original tumor tissue by immunohistochemistry. This cell line may be useful for studying the chemoresistant mechanisms of CCC and exploring novel therapeutic targets such as the ARID1A-related signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Scully RE. World Health Organization classification and nomenclature of ovarian cancer. Natl Cancer Inst Monogr. 1975;42:5–7.

    CAS  PubMed  Google Scholar 

  2. Itamochi H, Kigawa J, Terakawa N. Mechanisms of chemoresistance and poor prognosis in ovarian clear cell carcinoma. Cancer Sci. 2008;99:653–8.

    Article  CAS  PubMed  Google Scholar 

  3. Vlahos NF, Kalampokas T, Fotiou S. Endometriosis and ovarian cancer: a review. Gynecol Endocrinol. 2010;26:213–9.

    Article  PubMed  Google Scholar 

  4. Jimbo H, Yoshikawa H, Onda T, Yasugi T, Sakamoto A, Taketani Y. Prevalence of ovarian endometriosis in epithelial ovarian cancer. Int J Gynaecol Obstet. 1997;59:245–50.

    Article  CAS  PubMed  Google Scholar 

  5. Ohkawa K, Amasaki H, Terashima Y, Aizawa S, Ishikawa E. Clear cell carcinoma of the ovary: light and electron microscopic studies. Cancer. 1977;40:3019–29.

    Article  CAS  PubMed  Google Scholar 

  6. Sugiyama T, Kamura T, Kigawa J, et al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer. 2000;88:2584–9.

    Article  CAS  PubMed  Google Scholar 

  7. Takano M, Kikuchi Y, Yaegashi N, et al. Clear cell carcinoma of the ovary: a retrospective multicentre experience of 254 patients with complete surgical staging. Br J Cancer. 2006;94:1369–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pectasides D, Fountzilas G, Aravantinos G, et al. Advanced stage clear-cell epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol Oncol. 2006;102:285–91.

    Article  PubMed  Google Scholar 

  9. Mackay HJ, Brady MF, Oza AM, et al. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int J Gynecol Cancer. 2010;20:945–52.

    Article  PubMed  Google Scholar 

  10. Fukunaga M, Nomura K, Ishikawa E, Ushigome S. Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology. 1997;30:249–55.

    Article  CAS  PubMed  Google Scholar 

  11. Itamochi H, Oumi N, Oishi T, et al. Loss of ARID1A expression is associated with poor prognosis in patients with stage I/II clear cell carcinoma of the ovary. Int J Clin Oncol. 2015;20:967–73.

    Article  CAS  PubMed  Google Scholar 

  12. Jones S, Wang TL, Shih Ie M, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010;330:228–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wiegand KC, Shah SP, Al-Agha OM, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010;363:1532–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ho L, Crabtree GR. Chromatin remodelling during development. Nature. 2010;463:474–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609–15.

    Article  Google Scholar 

  16. Kuo KT, Mao TL, Jones S, et al. Frequent activating mutations of PIK3CA in ovarian clear cell carcinoma. Am J Pathol. 2009;174:1597–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Itamochi H, Kato M, Nishimura M, et al. Establishment and characterization of a novel ovarian clear cell adenocarcinoma cell line, TU-OC-1, with a mutation in the PIK3CA gene. Hum Cell. 2013;26:121–7.

    Article  CAS  PubMed  Google Scholar 

  18. Park JG, Kramer BS, Steinberg SM, et al. Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. Cancer Res. 1987;47:5875–9.

    CAS  PubMed  Google Scholar 

  19. Gorai I, Nakazawa T, Miyagi E, Hirahara F, Nagashima Y, Minaguchi H. Establishment and characterization of two human ovarian clear cell adenocarcinoma lines from metastatic lesions with different properties. Gynecol Oncol. 1995;57:33–46.

    Article  CAS  PubMed  Google Scholar 

  20. Ohta I, Gorai I, Miyamoto Y, et al. Cyclophosphamide and 5-fluorouracil act synergistically in ovarian clear cell adenocarcinoma cells. Cancer Lett. 2001;162:39–48.

    Article  CAS  PubMed  Google Scholar 

  21. Sato S, Itamochi H, Kigawa J, et al. Combination chemotherapy of oxaliplatin and 5-fluorouracil may be an effective regimen for mucinous adenocarcinoma of the ovary: a potential treatment strategy. Cancer Sci. 2009;100:546–51.

    Article  CAS  PubMed  Google Scholar 

  22. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489–501.

    Article  CAS  PubMed  Google Scholar 

  23. Itamochi H. Targeted therapies in epithelial ovarian cancer: molecular mechanisms of action. World J Biol Chem. 2010;1:209–20.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Itamochi H, Kigawa J, Sugiyama T, Kikuchi Y, Suzuki M, Terakawa N. Low proliferation activity may be associated with chemoresistance in clear cell carcinoma of the ovary. Obstet Gynecol. 2002;100:281–7.

    PubMed  Google Scholar 

  25. Itamochi H, Kigawa J, Akeshima R, et al. Mechanisms of cisplatin resistance in clear cell carcinoma of the ovary. Oncology. 2002;62:349–53.

    Article  CAS  PubMed  Google Scholar 

  26. Dimanche-Boitrel MT, Pelletier H, Genne P, et al. Confluence-dependent resistance in human colon cancer cells: role of reduced drug accumulation and low intrinsic chemosensitivity of resting cells. Int J Cancer. 1992;50:677–82.

    Article  CAS  PubMed  Google Scholar 

  27. Barcellos-Hoff MH, Marton LJ, Deen DF. Differential drug sensitivity conferred by growth status detected in a mixed population of cycling and noncycling cells. Cancer Res. 1990;50:3551–5.

    CAS  PubMed  Google Scholar 

  28. Sato S, Itamochi H. Ovarian cancer and drug resistance. Curr Obstet Gynecol Rep. 2015;4:18–25.

    Article  Google Scholar 

  29. Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS ONE. 2013;8:e55119.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011;11:481–92.

    Article  CAS  PubMed  Google Scholar 

  31. Bitler BG, Fatkhutdinov N, Zhang R. Potential therapeutic targets in ARID1A-mutated cancers. Expert Opin Ther Targets. 2015;19:1419–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yamaguchi K, Matsumura N, Mandai M, Baba T, Konishi I, Murphy SK. Epigenetic and genetic dispositions of ovarian carcinomas. Oncoscience. 2014;1:574–9.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Katagiri A, Nakayama K, Rahman MT, et al. Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol. 2012;25:282–8.

    CAS  PubMed  Google Scholar 

  34. van der Heijden MS, Bernards R. Inhibition of the PI3K pathway: hope we can believe in? Clin Cancer Res. 2010;16:3094–9.

    Article  PubMed  Google Scholar 

  35. Samartzis EP, Gutsche K, Dedes KJ, Fink D, Stucki M, Imesch P. Loss of ARID1A expression sensitizes cancer cells to PI3K- and AKT-inhibition. Oncotarget. 2014;5:5295–303.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Samartzis EP, Noske A, Dedes KJ, Fink D, Imesch P. ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas. Int J Mol Sci. 2013;14:18824–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wiegand KC, Hennessy BT, Leung S, et al. A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. BMC Cancer. 2014;14:120.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Brosh R, Rotter V. When mutants gain new powers: news from the mutant p53 field. Nat Rev Cancer. 2009;9:701–13.

    CAS  PubMed  Google Scholar 

  39. Okada S, Tsuda H, Takarabe T, Yoshikawa H, Taketani Y, Hirohashi S. Allelotype analysis of common epithelial ovarian cancers with special reference to comparison between clear cell adenocarcinoma with other histological types. Jpn J Cancer Res. 2002;93:798–806.

    Article  CAS  PubMed  Google Scholar 

  40. Ho ES, Lai CR, Hsieh YT, et al. p53 mutation is infrequent in clear cell carcinoma of the ovary. Gynecol Oncol. 2001;80:189–93.

    Article  CAS  PubMed  Google Scholar 

  41. Itamochi H, Kigawa J, Kanamori Y, et al. Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential treatment strategy. Mol Cancer Ther. 2007;6:227–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka-City, Iwate, 020-8505, Japan

    Seiya Sato, Hiroaki Itamochi, Youhei Chiba & Toru Sugiyama

  2. Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago-City, Tottori, 683-8504, Japan

    Nao Oumi, Tetsuro Oishi, Muneaki Shimada, Shinya Sato, Jun Chikumi, Michiko Nonaka, Akiko Kudoh, Hiroaki Komatsu & Tasuku Harada

Authors
  1. Seiya Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroaki Itamochi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nao Oumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Youhei Chiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tetsuro Oishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Muneaki Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shinya Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jun Chikumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michiko Nonaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Akiko Kudoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hiroaki Komatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Tasuku Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Toru Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroaki Itamochi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sato, S., Itamochi, H., Oumi, N. et al. Establishment and characterization of a novel ovarian clear cell carcinoma cell line, TU-OC-2, with loss of ARID1A expression. Human Cell 29, 181–187 (2016). https://doi.org/10.1007/s13577-016-0138-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-016-0138-6

Keywords

Search

Navigation