Skip to main content
SpringerLink
Log in

Relevance of ER to the development of endometrial hyperplasia and adenocarcinoma

  • Published:
Breast Cancer Aims and scope Submit manuscript

Abstract

Estrogen has an important role in both the etiology and treatment of hormone-dependent endometrial cancers, although the mechanism remains elusive. To define the role of estrogen-mediated signaling we investigated the biological significance of estrogen receptors (ER) in NIH3T3 cell transformation via the [12Val] K-Ras mutant. This mutant enhanced the steady state level and transcriptional activity of ER. In addition, overexpression of both wild type K-Ras and ER transformed NIH3T3 cells. Co-expression of the progesterone receptor (PR) with mutant K-Ras led to suppression of tumorigenicity and inhibition of ER activation. The antisense oligomers complementary to ER suppressed proliferation and transformed phenotypes of K12V cells. These observations support the importance of ER in Ras-mediated cell transformation.

To address whether ER activation is also important in the development of human endometrial cancers, we investigated ER and PR expression levels in premalignant and malignant endometrial lesions. The results suggested the implication of ER abundance in endometrial hyperplasias, though modulation of PR expression by ER was retained. Gl adenocarcinoma also expressed higher levels of ER while PR modulation by ER was abrogated. These data implied the importance of ER activities in endometrial hyperplasia and Gl adenocarcinoma development.

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.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ER:

Estrogen receptor

PR:

Progesterone receptor

MAPK:

Mitogenactivated protein kinases

E2:

17 β-Estradiol

P:

Progesterone

ERE:

Estrogen responsive element

References

  1. Vojek AB, Hollenberg SM, Cooper JA: Mammalian ras interacts directly with serine/threonine kinase Raf.Cell 74:205–214, 1993.

    Article  Google Scholar 

  2. Warne R Viciana R Downward J: Direct interaction of ras and the aminoterminal region of Raf-1 in vitro.Nature 364:352–355, 1993.

    Article  PubMed  CAS  Google Scholar 

  3. Zhang XF, Settleman J, Kyriakis JM,et al: Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1.Nature 364:308–313, 1993.

    Article  PubMed  CAS  Google Scholar 

  4. Coezy E, Borgna JL, Rochefort H: Tamoxifen and metabolites in MCF-7 cells; Correlation between binding to estrogen receptor and inhibition of cell growth.Cancer Res 42:317–323, 1982.

    PubMed  CAS  Google Scholar 

  5. Petrangeli E, Lubrano C, Ortolani F,et al: Estrogen receptors; New perspectives in breast cancer management.J Steroid Biochem Mol Biol 49:327–331, 1994.

    Article  PubMed  CAS  Google Scholar 

  6. Kato S, Endoh H, Masuhiro Y,et al: Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase.Science 270:1491–1494, 1995.

    Article  PubMed  CAS  Google Scholar 

  7. Kato K, Ueoka Y, Kato K,et al: Contribution of enhanced transcriptional activation by ER to [12Val] K-Ras mediated NIH3T3 cell transformation.Oncogene 15:3037–3046, 1997.

    Article  PubMed  CAS  Google Scholar 

  8. Meyer M-E, Gronemeyer H, Turcotte B,et al: Steroid hormone receptors compete for factors that mediate their enhancer function.Cell 57:433–442, 1989.

    Article  PubMed  CAS  Google Scholar 

  9. Rose PG: Endometrial carcinoma.N Engl J Med 335:640–649, 1996.

    Article  PubMed  CAS  Google Scholar 

  10. Enomoto T, Inoue M, Perantoni AO,et al: K-ras activation in neoplasms of the human female reproductive tract.Cancer Res 50:6139–6145, 1990.

    PubMed  CAS  Google Scholar 

  11. Enomoto T, Inoue M, Perantoni AO,et al: K-ras activation in premalignant and malignant epithelial lesion of the human uterus.Cancer Res 51:5308–5314, 1991.

    PubMed  CAS  Google Scholar 

  12. Sasaki H, Nishii H, Takahashi H,et al: Mutation of the Ki-ras protooncogene in human endometrial hyperplasia and carcinoma.Cancer Res 53:1906–1910, 1993.

    PubMed  CAS  Google Scholar 

  13. Caduff RF, Johnston CM, Frank TS: Mutation of the Ki-ras oncogene in carcinoma of the endometrium.Am J Pathol 146:182–188, 1995.

    PubMed  CAS  Google Scholar 

  14. Nisolle M, Menten Y, C-Roux F,et al: Immunohisto-chemical analysis of estrogen and progesterone receptors in endometrium and peritoneal endometriosis; A new quantitative method.Fertil Steril 62:751–759, 1994.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Reproductive Physiology and Endocrinology, Kyushu

    Kiyoko Kato, Shinji Horiuchi, Yasuhisa Terao, Yousuke Ueoka, Jun-ichi Nishida & Norio Wake

  2. Pathology, Medical Institute of Bioregulation, Kyushu University, Kyushu

    Daisuke Mori & Yasuji Yoshikawa

Authors
  1. Kiyoko Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinji Horiuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasuhisa Terao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yousuke Ueoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun-ichi Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daisuke Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasuji Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Norio Wake
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Kato, K., Horiuchi, S., Terao, Y. et al. Relevance of ER to the development of endometrial hyperplasia and adenocarcinoma. Breast Cancer 6, 312–319 (1999). https://doi.org/10.1007/BF02966446

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02966446

Key words

Search

Navigation