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Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells

Prostate Cancer and Prostatic Diseases volume 4, pages 81–91 (2001)Cite this article

Abstract

Preclinical models for the identification of prostate cancer chemoprevention agents are lacking. Based upon the notion that clinically useful chemoprevention agents should exhibit selective activity against early stage disease, studies were undertaken to assess whether chemoprevention agents selectively inhibited the growth of early stage prostate cancer, as compared to late stage cancer. First, a series of cell and molecular studies were performed, which, when taken together, validated the use of a panel of prostate cell lines as a model of the different stages of carcinogenesis. Next, therapeutic responsiveness to ten different cytotoxic or chemoprevention agents was evaluated. Chemoprevention agents exhibited selective activity against normal and early transformed prostate tissue, whereas cytotoxic agents were non-specific. Selective activity against early versus advanced prostate cancer cells is identified as a potential screening method for chemoprevention agents.

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References

  1. Oesterling JE, Fuks Z, Lee CT, Scher HI. Cancer of the prostate. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer: Principals and Practice of Oncology Vol 1 Lippincott-Raven: New York 1997 1322–1385.

    Google Scholar 

  2. Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer Statistics, 2000. CA Cancer J Clin 2000 50 7–33.

    Article  CAS  Google Scholar 

  3. Oh WK, Kantoff PW. Management of hormone refractory prostate cancer: current standards and future prospects [see comments]. J Urol 1998 160 1220–1229.

    Article  CAS  Google Scholar 

  4. Lara PN Jr, Kung HJ, Gumerlock PH, Meyers FJ. Molecular biology of prostate carcinogenesis. Crit Rev Oncol Hematol 1999 32 197–208.

    Article  Google Scholar 

  5. Sciavolino PJ, Abate-Shen C. Molecular biology of prostate development and prostate cancer. Ann Med 1998 30 357–368.

    Article  CAS  Google Scholar 

  6. Carter HB, Piantadosi S, Isaacs JT. Clinical evidence for and implications of the multistep development of prostate cancer. J Urol 1990 143 742–746.

    Article  CAS  Google Scholar 

  7. Bostwick DG. Prostatic intraepithelial neoplasia is a risk factor for cancer. Semin Urol Oncol 1999 17 187–198.

    CAS  PubMed  Google Scholar 

  8. Vogelstein B, Kinzler KW. The multistep nature of cancer. Trends Genet 1993 9 138–141.

    Article  CAS  Google Scholar 

  9. Bishop JM. Molecular themes in oncogenesis. Cell 1991 64 235–248.

    Article  CAS  Google Scholar 

  10. Royai R, Lange PH, Vessella R. Preclinical models of prostate cancer. Semin Oncol 1996 23 35–40.

    CAS  PubMed  Google Scholar 

  11. Kelloff GJ et al Progress in cancer chemoprevention. Ann N Y Acad Sci 1999 889 1–13.

    Article  CAS  Google Scholar 

  12. Kozlowski JM et al Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res 1984 44 3522–3529.

    CAS  PubMed  Google Scholar 

  13. 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  Google Scholar 

  14. Bright RK et al Generation and genetic characterization of immortal human prostate epithelial cell lines derived from primary cancer specimens. Cancer Res 1997 57 995–1002.

    CAS  PubMed  Google Scholar 

  15. Bergan R et al Electroporation of synthetic oligodeoxynucleotides: a novel technique for ex vivo bone marrow purging. Blood 1996 88 731–741.

    CAS  PubMed  Google Scholar 

  16. Schwartz GN et al Growth inhibition of chronic myelogenous leukemia cells by ODN-1, an aptameric inhibitor of p210bcr-abl tyrosine kinase activity. Antisense Nucleic Acid Drug Dev 1998 8 329–339.

    Article  CAS  Google Scholar 

  17. Rohlff C et al Growth inhibition of prostate cancer cells by tamoxifen is associated with protein kinase C inhibition and induction of p21 waf1/cip1 Prostate 1998 37 51–59.

    Article  CAS  Google Scholar 

  18. 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  Google Scholar 

  19. Bergan R, Connell Y, Fahmy B, Neckers L. Electroporation enhances c-myc antisense oligodeoxynucleotide efficacy. Nucleic Acids Res 1993 21 3567–3573.

    Article  CAS  Google Scholar 

  20. Bergan RC, Kyle E, Connell Y, Neckers L. Inhibition of protein-tyrosine kinase activity in intact cells by the aptameric action of oligodeoxynucleotides. Antisense Res Dev 1995 5 33–38.

    Article  CAS  Google Scholar 

  21. Bergan R et al Aptameric inhibition of p210bcr-abl tyrosine kinase autophosphorylation by oligodeoxynucleotides of defined sequence and backbone structure. Nucleic Acids Res 1994 22 2150–2154.

    Article  CAS  Google Scholar 

  22. Dakhama A, Macek V, Hogg JC, Hegele RG. Amplification of human beta-actin gene by the reverse transcriptase-polymerase chain reaction: implications for assessment of RNA from formalin-fixed, paraffin-embedded material. J Histochem Cytochem 1996 44 1205–1207.

    Article  CAS  Google Scholar 

  23. Jaakkola S et al Detection of prostatic cells in peripheral blood: correlation with serum concentrations of prostate-specific antigen [see comments]. Clin Chem 1995 41 182–186.

    CAS  PubMed  Google Scholar 

  24. Culig Z et al DNA sequence of the androgen receptor in prostatic tumor cell lines and tissue specimens assessed by means of the polymerase chain reaction. Prostate 1993 22 11–22.

    Article  CAS  Google Scholar 

  25. Roberts AB. Molecular and cell biology of TGF-beta. Miner Electrolyte Metab 1998 24 111–119.

    Article  CAS  Google Scholar 

  26. Sporn MB, Roberts AB, Wakefield LM, de Crombrugghe B. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol 1987 105 1039–1045.

    Article  CAS  Google Scholar 

  27. Webber MM, Bello D, Quader S. Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part I. Cell markers and immortalized nontumorigenic cell lines. Prostate 1996 29 386–394.

    Article  CAS  Google Scholar 

  28. Peehl DM. Culture of human prostatic epithelial cells. In: RA Freshney (ed). Culture of Epithelial Cells (Culture of Specialized Cells) John Wiley & Sons: New York 1992 159–180.

    Google Scholar 

  29. Webber MM et al Prostate specific antigen and androgen receptor induction and characterization of an immortalized adult human prostatic epithelial cell line Carcinogenesis 1996 17 1641–1646.

    Article  CAS  Google Scholar 

  30. Bello D et al Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18. Carcinogenesis 1997 18 1215–1223.

    Article  CAS  Google Scholar 

  31. Cussenot O et al Immortalization of human adult normal prostatic epithelial cells by liposomes containing large T-SV40 gene. J Urol 1991 146 881–886.

    Article  CAS  Google Scholar 

  32. Weijerman PC et al Lipofection-mediated immortalization of human prostatic epithelial cells of normal and malignant origin using human papillomavirus type 18 DNA. Cancer Res 1994 54 5579–5583.

    CAS  PubMed  Google Scholar 

  33. Mickey DD et al Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice. Cancer Res 1977 37 4049–4058.

    CAS  PubMed  Google Scholar 

  34. Kaighn ME et al Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 1979 17 16–23.

    CAS  PubMed  Google Scholar 

  35. Jenkins RB, Qian J, Lieber MM, Bostwick DG. Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. Cancer Res 1997 57 524–531.

    CAS  PubMed  Google Scholar 

  36. Tremblay L, Aprikian A, Chevalier S. Expression of focal adhesion kinase in prostate cancer. Proc Am Ass Cancer Res 1995 36 64.

    Google Scholar 

  37. Webber MM, Bello D, Quader S. Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part 3. Oncogenes, suppressor genes, and applications. Prostate 1997 30 136–142.

    Article  CAS  Google Scholar 

  38. Kim IY et al Loss of expression of transforming growth factor β type I and type II receptors correlates with tumor grade in human prostate cancer tissues. Clinical Cancer Res 1996 2 1255–1261.

    CAS  Google Scholar 

  39. Sehgal I, Baley PA, Thompson TC. Transforming growth factor betal stimulates contrasting responses in metastatic vs primary mouse prostate cancer-derived cell lines in vitro Cancer Res 1996 56 3359–3365.

    CAS  PubMed  Google Scholar 

  40. Wilding G et al Differential effects of transforming growth factor beta on human prostate cancer cells in vitro Mol Cell Endocrinol 1989 62 79–87.

    Article  CAS  Google Scholar 

  41. Steiner MS, Zhou ZZ, Tonb DC, Barrack ER. Expression of transforming growth factor-beta 1 in prostate cancer. Endocrinology 1994 135 2240–2247.

    Article  CAS  Google Scholar 

  42. Eastham JA et al Transforming growth factor-beta 1: comparative immunohistochemical localization in human primary and metastatic prostate cancer. Lab Invest 1995 73 628–635.

    CAS  PubMed  Google Scholar 

  43. Tu H, Jacobs SC, Borkowski A, Kyprianou N. Incidence of apoptosis and cell proliferation in prostate cancer: relationship with TGF-beta l and bcl-2 expressing. Int J Cancer 1996 69 357–363.

    Article  CAS  Google Scholar 

  44. Perry KT, Anthony CT, Steiner MS. Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in normal and malignant human prostate. Prostate 1997 33 133–140.

    Article  CAS  Google Scholar 

  45. Ablin RJ. A retrospective and prospective overview of prostate-specific antigen. J Cancer Res Clin Oncol 1997 123 583–594.

    Article  CAS  Google Scholar 

  46. Culig Z et al Expression, structure, and function of androgen receptor in advanced prostatic carcinoma. Prostate 1998 35 63–70.

    Article  CAS  Google Scholar 

  47. Kastan MB. Molecular biology of cancer: the cell cycle. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer: Principals and Practice of Oncology 1. Lippincott-Raven: New York 1997 121–134.

    Google Scholar 

  48. Fidler IJ. Molecular biology of cancer: invasion and metastasis. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer: Principals and Practice of Oncology 1. Lippincott-Raven Publishers: Philadelphia 1997 135–152.

    Google Scholar 

  49. Bender RA, Hamel E, Hande KR. Plant alkaloids. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer Chemotherapy: Principles and Practice JB Lippincott: Philadelphia 1990 253–275.

    Google Scholar 

  50. Myers CE, Chabner BA. Anthracyclines. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer Chemotherapy: Principles and Practice JB Lippincott: Philadelphia 1990 357–381.

    Google Scholar 

  51. NIH Development. Clinical development plan: 1-perillyl alcohol. J Cell Biochem 1996 26 137–148.

    Google Scholar 

  52. Stewart CF, Ratain MJ. Topoisomerase interactive agents. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer: Principals and Practice of Oncology 1. Lippincott-Raven: New York 1997 452–467.

    Google Scholar 

  53. Rowinsky EK, Donehower RC. Antimicrotubule agents. In: DeVita VT, Hellman S, Rosenberg SA (eds). Cancer: Principals and Practice of Oncology 1. Lippincott-Raven: New York 1997 467–482.

    Google Scholar 

  54. Steele VE, Pereira MA, Sigman CC, Kelloff GJ. Cancer chemoprevention agent development strategies for genistein. J Nutr 1995 125 (Suppl 3): 713S–716S.

    PubMed  Google Scholar 

  55. Bergan RC et al A phase II study of high dose tamoxifen in patients with hormone refractory prostate cancer. Clinical Cancer Research 1999 5 2366–2373.

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Northwest University Medical School and the Robert H. Lurie Cancer Center of Northwestern University, Chicago, USA

    YQ Liu & RC Bergan

  2. Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    E Kyle, S Patel, F Hakim & MV Blagosklonny

  3. Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    F Housseau

  4. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    R Lieberman

  5. Department of Pathology, Northwestern University Medical School and the Robert H. Lurie Cancer Center of Northwestern University, Chicago, USA

    M Pins

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  1. YQ Liu
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Liu, Y., Kyle, E., Patel, S. et al. Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells. Prostate Cancer Prostatic Dis 4, 81–91 (2001). https://doi.org/10.1038/sj.pcan.4500506

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  • DOI: https://doi.org/10.1038/sj.pcan.4500506

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