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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.

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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 

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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

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  1. M Slater
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  2. D Brown
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  3. A Husband
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Correspondence to M Slater.

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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

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

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