Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
January 2013 Volume 5 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January 2013 Volume 5 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate

  • Authors:
    • Shujun Zhao
    • Genxia Li
    • Li Yang
    • Lei Li
    • Hongyu Li
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China
  • Pages: 139-144
    |
    Published online on: October 17, 2012
       https://doi.org/10.3892/ol.2012.975
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Progestins, particularly medroxyprogesterone acetate (MPA), have for a long time been used as conservative treatment for young patients with clinical stage I, grade I endometrial carcinoma. However, more than 30% of patients with endometrial adenocarcinoma display resistance to endocrine therapies at the time of presentation and most cancer patients that initially respond to progestin treatment will at some point develop resistance, resulting in tumor progression. The cellular mechanisms underlying acquired resistance to progestin are poorly understood. In order to investigate the molecular mechanisms whereby human endometrial adenocarcinoma develops resistance to progestin therapy, we have undertaken to develop human endometrial adenocarcinoma cell lines that are resistant to the growth-inhibitory effects of progestins in vitro. A progestin‑resistant subcell line of Ishikawa cells was developed from Ishikawa human endometrial adenocarcinoma cells by stepwise selection in increasing concentrations of the synthetic progestin, MPA, over ten months. The doubling time of the progestin‑resistant cells (34.18±3.15 h) grown routinely in the medium containing 10 µM MPA was not significantly different from the doubling time of the parent Ishikawa cells (35.14±2.68 h) grown in the absence of MPA (t=‑0.331, P=0.762). Moreover, the effect of treatment with MPA shifted from suppression of growth and invasiveness, as observed in the parent Ishikawa cells, to stimulation of growth and invasiveness in the progestin‑resistant Ishikawa cells. The positive rates of estrogen receptor a (ERα) and progesterone receptor B (PRB) of the progestin‑resistant Ishikawa cells were significantly reduced, whilst the positive rate of ERβ was significantly enhanced compared to the parent Ishikawa cells. These differences were statistically significant (P<0.05). Our results indicate that long‑term treatment with MPA in Ishikawa cells may give rise to a resistance effect to MPA. When the resistant subtype is acquired, treatment with MPA enhances cancer cell proliferation and invasiveness. The imbalance of ER and PR subtypes may contribute to the mechanisms involved in progestin resistance. Determination of the subtypes of ER and PR may provide important additional information on the hormone sensitivity of endometrial carcinoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kim JJ and Chapman-Davis E: Role of progesterone in endometrial cancer. Semin Reprod Med. 28:81–90. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Jadoul P and Donnez J: Conservative treatment may be beneficial for young women with atypical endometrial hyperplasia or endometrial adenocarcinoma. Fertil Steril. 80:1315–1324. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Cade TJ, Quinn MA, Rome RM and Neesham D: Progestogen treatment options for early endometrial cancer. BJOG. 117:879–884. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Niwa K, Tagami K, Lian Z, Onogi K, Mori H and Tamaya T: Outcome of fertility-preserving treatment in young women with endometrial carcinomas. BJOG. 112:317–320. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Laurelli G, Di Vagno G, Scaffa C, Losito S, Del Giudice M and Greggi S: Conservative treatment of early endometrial cancer: preliminary results of a pilot study. Gynecol Oncol. 120:43–46. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Murphy LC, Dotzlaw H, Wong MS, Miller T and Murphy LJ: Mechanisms involved in the evolution of progestin resistance in human breast cancer cells. Cancer Res. 51:2051–2057. 1991.PubMed/NCBI

7 

Coldham NG, Patel K and Braunsberg H: Hormone and cytotoxic drug responsiveness of cultured human breast cancer cells resistant to specific hormones. Int J Cancer. 45:712–718. 1990. View Article : Google Scholar : PubMed/NCBI

8 

Herman ME and Katzenellembogen BS: Response-specific antiestrogen resistance in a newly characterized MCF-7 human breast cancer cell line resulting from long-term exposure to trans-hydroxytamoxifen. J Steroid Biochem Mol Biol. 59:121–134. 1996. View Article : Google Scholar

9 

Nishida M, Kasahara K, Kaneko M, Iwasaki H and Hayashi K: Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors. Nippon Sanka Fujinka Gakkai Zasshi. 37:1103–1111. 1985.PubMed/NCBI

10 

Ito K, Utsunomiya H, Yaegashi N and Sasano H: Biological roles of estrogen and progesterone in human endometrial carcinoma - new developments in potential endocrine therapy for endometrial cancer. Endocr J. 54:667–679. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Zaino RJ, Clarke CL, Mortel R and Satyaswaroop PG and Satyaswaroop PG: Heterogeneity and progesterone-receptor distribution in endometrial adenocarcinoma. Cancer Res. 48:1889–1895. 1988.

12 

Jongen V, Briët J, de Jong R, ten Hoor K, Boezen M, van der Zee A and Nijman H: Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol. 112:537–542. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Stoian SC, Simionescu C, Mărgăritescu C, Stepan A and Nurciu M: Endometrial carcinomas: correlation between ER, PR, Ki67 status and histopathological prognostic parameters. Rom J Morphol Embryol. 52:631–636. 2011.PubMed/NCBI

14 

Hall JM and McDonnell DP: The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology. 140:5566–5578. 1999.

15 

Ali SH, O’Donnell AL, Mohamed S, Mousa S and Dandona P: Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line Ishikawa: inhibition of growth and angiogenic factors. Gynecol Oncol. 95:637–645. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Ali SH, O’Donnell AL, Balu D, Pohl MB, Seyler MJ, Mohamed S, Mousa S and Dandona P: Estrogen receptor-alpha in the inhibition of cancer growth and angiogenesis. Cancer Res. 60:7094–7098. 2000.PubMed/NCBI

17 

Miyamoto T, Watanabe J, Hata H, Jobo T, Kawaguchi M, Hattori M, Saito M and Kuramoto H: Significance of progesterone receptor-A and -B expressions in endometrial adenocarcinoma. J Steroid Biochem Mol Biol. 2:110–118. 2004.PubMed/NCBI

18 

Smid-Koopman E, Kuhne LC, Hanekamp EE, Gielen SC, De Ruiter PE, Grootegoed JA, Helmerhorst TJ, Burger CW, Brinkmann AO, Huikeshoven FJ and Blok LJ: Progesterone-induced inhibition of growth and differential regulation of gene expression in PRA- and/or PRB-expressing endometrial cancer cell lines. J Soc Gynecol Invest. 12:285–292. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Dai D, Wolf DM, Litman ES, White MJ and Leslie KK: Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res. 62:881–886. 2002.

20 

Aghajanova L, Velarde MC and Giudice LC: Altered gene expression profiling in endometrium: evidence for progesterone resistance. Semin Reprod Med. 28:51–58. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Arpino G, Weiss H, Lee AV, Schiff R, De Placido S, Osborne CK and Elledge RM: Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 97:1254–1261. 2005. View Article : Google Scholar

22 

Wang S, Pudney J, Song J, Mor G, Schwartz PE and Zheng W: Mechanisms involved in the evolution of progestin resistance in human endometrial hyperplasia - precursor of endometrial cancer. Gynecol Oncol. 88:108–117. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Yang S, Thiel KW and Leslie KK: Progesterone: the ultimate endometrial tumor suppressor. Trends Endocrinol Metab. 22:145–152. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Engelsen IB, Stefansson IM, Akslen LA and Salvesen HB: GATA3 expression in estrogen receptor alpha-negative endometrial carcinomas identifies aggressive tumors with high proliferation and poor patient survival. Am J Obstet Gynecol. 199:543–547. 2008. View Article : Google Scholar

25 

Rubel CA, Jeong JW, Tsai SY, Lydon JP and Demayo FJ: Epithelial-stromal interaction and progesterone receptors in the mouse uterus. Semin Reprod Med. 28:27–35. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao S, Li G, Yang L, Li L and Li H: Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate. Oncol Lett 5: 139-144, 2013.
APA
Zhao, S., Li, G., Yang, L., Li, L., & Li, H. (2013). Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate. Oncology Letters, 5, 139-144. https://doi.org/10.3892/ol.2012.975
MLA
Zhao, S., Li, G., Yang, L., Li, L., Li, H."Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate". Oncology Letters 5.1 (2013): 139-144.
Chicago
Zhao, S., Li, G., Yang, L., Li, L., Li, H."Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate". Oncology Letters 5, no. 1 (2013): 139-144. https://doi.org/10.3892/ol.2012.975
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao S, Li G, Yang L, Li L and Li H: Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate. Oncol Lett 5: 139-144, 2013.
APA
Zhao, S., Li, G., Yang, L., Li, L., & Li, H. (2013). Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate. Oncology Letters, 5, 139-144. https://doi.org/10.3892/ol.2012.975
MLA
Zhao, S., Li, G., Yang, L., Li, L., Li, H."Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate". Oncology Letters 5.1 (2013): 139-144.
Chicago
Zhao, S., Li, G., Yang, L., Li, L., Li, H."Response‑specific progestin resistance in a newly characterized Ishikawa human endometrial cancer subcell line resulting from long‑term exposure to medroxyprogesterone acetate". Oncology Letters 5, no. 1 (2013): 139-144. https://doi.org/10.3892/ol.2012.975
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team