Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

In the prostatic epithelium, dietary isoflavones from red clover significantly increase estrogen receptor β and E-cadherin expression but decrease transforming growth factor β1

Prostate Cancer and Prostatic Diseases volume 5, pages 16–21 (2002)Cite this article

Abstract

In mice fed a diet supplemented with red clover isoflavones the prostatic epithelium displays a significant increase in the production of estrogen receptor β and the adhesion protein E-cadherin but a decrease in transforming growth factor β1. These proteins are estrogenically-induced markers of proliferation, maintenance of histological architecture, preservation of cell phenotype and reduction of the potential for neoplastic and metastatic transformation. This study suggests that red clover isoflavones represent a non-toxic dietary treatment for prostatic hyperplasia and a reduction in the potential for neoplastic transformation.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

References

  1. Slater M et al. Detection of preneoplasia in histologically normal prostate biopsies. Prostate Cancer PD 2001 4: 92–96.

    Article  CAS  Google Scholar 

  2. Slater M, Barden JA, Murphy CR. . Tyrosine kinase A, autonomic transmitter receptors, but not innervation, are upregulated in the aging rat prostate. Acta Histochem 2000 102: 427–438.

    Article  CAS  PubMed  Google Scholar 

  3. Slater M, Murphy CR. . Detection of apoptotic DNA damage in prostate hyperplasia using tyramide-amplified avidin-HRP. Histochem J 1999 31: 747–749.

    Article  CAS  PubMed  Google Scholar 

  4. Lian FR et al. Genistein-Induced G(2)-M Arrest, P21 (Waf1) upregulation, and apoptosis in a non-small-cell lung cancer cell line. Nutrition & Cancer 1998 31: 184–191.

    Article  CAS  Google Scholar 

  5. Muir C et al. Cancer Incidence in 5 Continents. International Agency for Research on Cancer: Lyon 1987

    Google Scholar 

  6. Xue L et al. Induced hyperproliferation in epithelial cells of mouse prostate by a Western-style diet. Carcinogenesis 1997 18: 995–999.

    Article  CAS  PubMed  Google Scholar 

  7. Kolonel L, Hinds M, Hankin J. . Cancer patterns among migrant and native-born Japanese in Hawaii Japan Sci Soc Press Tokyo 1980 43: 327–340.

    Google Scholar 

  8. Kolonel LN et al. Role of diet in cancer incidence in Hawaii. Cancer Res 1983 43: 2397s–2402s.

    CAS  PubMed  Google Scholar 

  9. Parkin D et al. Cancer Incidence in 5 Continents. International agency for research on cancer. 1992 120: 5–19.

  10. Bergan R et al. Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin. Clin Exp Metastasis 1996 14: 389–398.

    Article  CAS  PubMed  Google Scholar 

  11. Yang CC et al. Differential tyrosine phosphorylation/activation of oncogenic proline-directed protein kinase F(A)/GSK-3alpha in well and poorly differentiated human prostate carcinoma cells. J Protein Chem 1998 17: 329–335.

    Article  CAS  PubMed  Google Scholar 

  12. Adlercreutz H, Mazur W. . Phyto-oestrogens and Western diseases. Ann Med 1997 29: 95–120.

    Article  CAS  PubMed  Google Scholar 

  13. Henderson BE, Feigelson HS. . Hormonal carcinogenesis. Carcinogenesis 2000 21: 427–433.

    Article  CAS  PubMed  Google Scholar 

  14. Ciocca D et al. The presence of an estrogen-regulated protein detected by monoclonal antibody in abnormal human endometrium. J Clin Endocrinol Met 1985 60: 137–143.

    Article  CAS  Google Scholar 

  15. Rhodes L et al. Estradiol causes a dose-dependent stimulation of prostate growth in castrated beagle dogs. Prostate 2000 44: 8–18.

    Article  CAS  PubMed  Google Scholar 

  16. Taylor AH, Al-Azzawi F. . Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol 2000 24: 145–155.

    Article  CAS  PubMed  Google Scholar 

  17. Saunders PT. . Oestrogen receptor beta (ER beta). Rev Reproduction 1998 3: 164–171.

    Article  CAS  Google Scholar 

  18. Pelletier G, Labrie C, Labrie F. . Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 2000 165: 359–370.

    Article  CAS  PubMed  Google Scholar 

  19. Lau KM et al. Expression of estrogen receptor (ER)-alpha and ER-beta in normal and malignant prostatic epithelial cells: regulation by methylation and involvement in growth regulation. Cancer Res 2000 60: 3175–3182.

    CAS  PubMed  Google Scholar 

  20. Gustafsson JA. . An update on estrogen receptors. Seminars in Perinatology 2000 24: 66–69.

    Article  CAS  PubMed  Google Scholar 

  21. Huggins C, Hodges C. . Studies of prostatic cancer. 1. The effects of castration as well as estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941 1: 293–297.

    CAS  Google Scholar 

  22. Robertson C et al. Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J Natl Cancer Inst 1996 88: 908–917.

    Article  CAS  PubMed  Google Scholar 

  23. Ahmed M et al. High dose intravenous oestrogen (fosfestrol) in the treatment of symptomatic, metastatic, hormone-refractory carcinoma of the prostate. Int J Urol Nephrol 1998 30: 159–164.

    Article  CAS  Google Scholar 

  24. Kim IY et al. Loss of expression of transforming growth factor-beta receptors is associated with poor prognosis in prostate cancer patients. Clin Cancer Res 1998 4: 1625–1630.

    CAS  PubMed  Google Scholar 

  25. Cardillo MR et al. Transforming growth factor-beta expression in prostate neoplasia. Analyt Quan Cytol Histol 2000 22: 1–10.

    CAS  Google Scholar 

  26. Gold LI. . The role for transforming growth factor-beta (TGF-beta) in human cancer. Crit Rev Oncogenesis 1999 10: 303–360.

    CAS  PubMed  Google Scholar 

  27. Royuela M et al. Transforming growth factor beta 1 and its receptor types I and II. Comparison in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma. Growth Factors 1998 16: 101–110.

    Article  CAS  PubMed  Google Scholar 

  28. Wolff JM et al. Serum concentrations of transforming growth factor-beta 1 in patients with benign and malignant prostatic diseases. Anticancer Res 1999 19: 2657–2659.

    CAS  PubMed  Google Scholar 

  29. Schneider HP, Jackisch C. . Potential benefits of estrogens and progestogens on breast cancer. Int J Fertility Womens Med 1998 43: 278–285.

    CAS  Google Scholar 

  30. Tang B et al. Loss of responsiveness to transforming growth factor beta induces malignant transformation of nontumorigenic rat prostate epithelial cells. Cancer Res 1999 59: 4834–4842.

    CAS  PubMed  Google Scholar 

  31. Slater M. . Dynamic interactions of the extracellular matrix. Histol Histopathol 1996 11: 175–180.

    CAS  PubMed  Google Scholar 

  32. Hazan RB et al. Exogenous expression of N-cadherin in breast cancer cells induces cell migration, invasion, and metastasis [published erratum appears in J Cell Biol 2000; Apr 3 149: following 236]. J Cell Biol 2000 148: 779–790.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Nuruki K et al. E-Cadherin but not N-Cadherin expression is correlated with the intracellular distribution of catenins in human hepatocellular carcinomas. Oncol Rep 1998 5: 1109–1114.

    CAS  PubMed  Google Scholar 

  34. Wijnhoven BP, Dinjens WN, Pignatelli M. . E-cadherin-catenin cell-cell adhesion complex and human cancer. Br J Surgery 2000 87: 992–1005.

    Article  CAS  Google Scholar 

  35. Cohen MB et al. Cellular adhesion molecules in urologic malignancies. Am J Clin Pathol 1997 107: 56–63.

    Article  CAS  PubMed  Google Scholar 

  36. Bussemakers MJ et al. Complex cadherin expression in human prostate cancer cells. Int J Cancer 2000 85: 446–450.

    Article  CAS  PubMed  Google Scholar 

  37. Blaschuk OW, Munro SB, Farookhi R. . E-cadherin, estrogens and cancer: is there a connection? Can J Oncol 1994 4: 291–301.

    CAS  PubMed  Google Scholar 

  38. Slater M. . Mitochondrial DNA damage assessment using fluorescence microscopy quantitation. J Histotechnol 1999 22: 17–21.

    Article  Google Scholar 

  39. Slater M, Murphy CR. . Thrombospondin is sequentially expressed and then de-expressed during early pregnancy in the rat uterus. Histochem J 1999 31: 471–475.

    Article  CAS  PubMed  Google Scholar 

  40. Slater M, Murphy CR. . Differential expression of insulin-like growth factors in the uterine epithelium and extracellular matrix during early pregnancy. Matrix Biol 1999 18: 579–584.

    Article  CAS  PubMed  Google Scholar 

  41. Dalu A et al. Genistein, a component of soy, inhibits the expression of the EGF and ErbB2/Neu receptors in the rat dorsolateral prostate. Prostate 1998 37: 36–43.

    Article  CAS  PubMed  Google Scholar 

  42. Kyle E et al. Genistein-induced apoptosis of prostate cancer cells is preceded by a specific decrease in focal adhesion kinase activity. Mol Pharmacol 1997 51: 193–200.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Biomedical Research, The University of Sydney, Australia

    M Slater

  2. Novogen Ltd, North Ryde, Australia

    D Brown & A Husband

  3. Department of Veterinary Anatomy and Pathology, The University of Sydney, Australia

    A Husband

Authors
  1. M Slater
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Husband
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Slater.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Slater, M., Brown, D. & Husband, A. In the prostatic epithelium, dietary isoflavones from red clover significantly increase estrogen receptor β and E-cadherin expression but decrease transforming growth factor β1. Prostate Cancer Prostatic Dis 5, 16–21 (2002). https://doi.org/10.1038/sj.pcan.4500546

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.pcan.4500546

Keywords

This article is cited by

Search

Advanced search

Quick links