Skip to main content

Advertisement

SpringerLink
Log in

Stem Cell Genes in Androgen-independent Prostate Cancer

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Despite recent advances in the detection and treatment of early stage prostate cancer, there remains little effective therapy for patients with locally advanced and/or metastatic disease. Although the majority of patients with advanced disease respond initially to androgen ablation therapy, most go on to develop androgen-independent tumors that are inevitably fatal. Therefore, understanding the mechanisms by which a hormone-sensitive tumor escapes hormonal control is critical to the development of effective therapeutic modalities. The study of the differentiation pathways of normal and abnormal prostate growth has led to the development of a stem cell model for prostate cancer [1–3]. Recent work discussed in this commentary suggests that prostate tumors resist apoptosis and proliferate by adopting features of normal prostatic stem/progenitor cells. Basal cells, the putative stem/progenitor cells of the prostate, possess the phenotype of androgen-independence as do most advanced prostate cancers. Therefore, the study of basal cells may prove critical to understanding prostate carcinogenesis and to the development of novel strategies for preventing and managing prostate cancer.

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

References

  1. Isaacs JT: Control of cell proliferation and cell death in the normal and neoplastic prostate: A stem cell model. In: Rodgers CH, Coffey DS, Cunha G, Grayhack JT, Hinman F, Horton R (eds), Benign Prostate Hyperplasia. Vol. II. pp 85-94. Bethesda, MD: NIH Publication No 87-2881, 1987

  2. Bonkhoff H, Stein U, Aumuller G, Remberger K: Differential expression of 5 alpha-reductase isoenzymes in the human prostate and prostatic carcinomas. Prostate 29: 261-7, 1996

    Article  PubMed  Google Scholar 

  3. Bonkhoff H: Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer. European Urology 30: 201-5, 1996

    PubMed  Google Scholar 

  4. Liu AY, True LD, LaTray L, Nelson PS, Ellis WJ, Vessella RL, Lange PH, Hood L, van den Engh G: Cell-cell interaction in prostate gene regulation and cytodifferentiation. Proc Natl Acad Sci USA 94: 10705-10, 1997

    Article  PubMed  Google Scholar 

  5. Aumuller G: Morphologic and endocrine aspects of prostatic functions. Prostate 4: 195-214, 1983

    PubMed  Google Scholar 

  6. Magi GC, Loda M: Molecular events in the early phases of prostate carcinogenesis. Eur Urol 30: 167-76, 1996

    PubMed  Google Scholar 

  7. Kyprianou N, Isaacs JT: Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 122: 552, 1988

    PubMed  Google Scholar 

  8. Bonkhoff H, Remberger K: Widespread distribution of nuclear androgen receptors in the basal cell layer of the normal and hyperplastic human prostate. Virchows Arch A Pathol Anat Histopathol 422: 35-8, 1993

    PubMed  Google Scholar 

  9. Bonkhoff H, Stein U, Remberger K: The proliferative function of basal cells in the normal and hyperplastic human prostate. Prostate 24: 114-8, 1994

    PubMed  Google Scholar 

  10. Isaacs JT, Coffey DS: Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl 2: 33-50, 1989

    Google Scholar 

  11. English HF, Santen RJ, Isaacs JT: Response of glandular versus basal rat ventral prostatic epithelial cells to androgen withdrawal and replacement. Prostate 11: 229-42, 1987

    PubMed  Google Scholar 

  12. Evans GS, Chandler JA: Cell proliferation studies in the rat prostate: II. The effects of castration and androgen-induced regeneration upon basal and secretory cell proliferation. Prostate 11: 339-51, 1987

    PubMed  Google Scholar 

  13. Bonkhoff H, Stein U, Remberger K: Multidirectional differentiation in the normal, hyperplastic, and neoplastic human prostate: simultaneous demonstration of cell-specific epithelial markers. Hum Pathol 25: 42-6, 1994

    Article  PubMed  Google Scholar 

  14. Bonkhoff H: Role of the basal cells in premalignant changes of the human prostate: a stem cell concept for the development of prostate cancer. Eur Urol 30: 201-5, 1996

    PubMed  Google Scholar 

  15. Bonkhoff H, Remberger K: Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: A stem cell model. Prostate 28: 98-106, 1996

    Article  PubMed  Google Scholar 

  16. Verhagen AP, Aalders TW, Ramaekers FC, Debruyne FM, Schalken JA: Differential expression of keratins in the basal and luminal compartments of rat prostatic epithelium during degeneration and regeneration. Prostate 13: 25-38, 1988

    PubMed  Google Scholar 

  17. Verhagen AP, Ramaekers FC, Aalders TW, Schaafsma HE, Debruyne FM, Schalken JA: Colocalization of basal and luminal cell-type cytokeratins in human prostate cancer. Cancer Res 52: 6182-7, 1992

    PubMed  Google Scholar 

  18. Xue Y, Smedts F, Debruyne FM, de la Rosette JJ, Schalken JA: Identification of intermediate cell types by keratin expression in the developing human prostate (published erratum appears in Prostate 1998 May; 35(2): 156). Prostate 34: 292-301, 1998

    Article  PubMed  Google Scholar 

  19. Robinson EJ, Neal DE, Collins AT: Basal cells are progenitors of luminal cells in primary cultures of differentiating human prostatic epithelium. Prostate 37: 149-60, 1998

    Article  PubMed  Google Scholar 

  20. Nagle RB, Ahmann FR, McDaniel KM, Paquin ML, Clark VA, Celniker A: Cytokeratin characterization of human prostatic carcinoma and its derived cell lines. Cancer Res 47: 281-6, 1987

    PubMed  Google Scholar 

  21. De Marzo MA, Nelson WG, Meeker AK, Coffey DS: Stem cell features of benign and malignant prostate epithelial cells. J Urol 1998

  22. Bonkhoff H, Stein U, Remberger K: Endocrine-paracrine cell types in the prostate and prostatic adenocarcinoma are postmitotic cells. Hum Pathol 26: 167-170, 1995

    Article  PubMed  Google Scholar 

  23. Klein KA, Reiter RE, Redula J, Moradi H, Zhu XL, Brothman AR, Lamb DJ, Marcelli M, Belldegrun A, Witte ON, Sawyers CL: Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. Nature Medicine 3: 402-8, 1997

    Article  PubMed  Google Scholar 

  24. Hobisch A, Culig Z, Radmayr C, Bartsch G., Klocker H, Hittmair A: Distant metastases from prostatic carcinoma express androgen receptor protein. Cancer Research 55: 3068-72, 1995

    PubMed  Google Scholar 

  25. Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP: Androgen receptor gene and hormonal therapy failure of prostate cancer. Am J Pathol 152: 1-9, 1998

    PubMed  Google Scholar 

  26. Kokontis JM, Hay N, Liao S: Progression of LNCaP prostate tumor cells during androgen deprivation: hormone-independent growth, repression of proliferation by androgen, and role for p27Kip1 in androgen-induced cell cycle arrest. Mol Endocrinol 12: 941-53, 1998

    Article  PubMed  Google Scholar 

  27. Visakorpi T, Hyytinen E, Doivisto P, Tanner M, Keinanen R, Palmberg C, Palotie A, Tammela T, Isola J, Kallioniemi OP: In vivoamplification of the androgen receptor gene and progression of human prostate cancer: Nature Gen 9: 401-406, 1995

    Article  PubMed  Google Scholar 

  28. Tilley WD, Buchanan G, Hickey TE, Bentel JM: Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res 2: 277-285, 1996

    PubMed  Google Scholar 

  29. Veldsholte J, Ris-Stalpers C, Kuiper G: A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys ResCom173: 534-540, 1990

    Google Scholar 

  30. Gaddipati JP, McLeod DG, Heidenberg HB, Sesterhenn IA, Finger MJ, JW, M, Srivastava S: Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers. Cancer Res 54: 2861-2864, 1994

    PubMed  Google Scholar 

  31. Hobisch A, Eder IE, Putz T, Horninger W, Bartsch G, Klocker H, Culig Z: Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor. Cancer Res 58: 4640-5, 1998

    PubMed  Google Scholar 

  32. Steiner MS: Review of peptide growth factors in benign prostatic hyperplasia dn urological malignancies. Journal of Urology 153: 1085-1096, 1995

    Article  PubMed  Google Scholar 

  33. McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LWK, Hsieh JT, Tu SM, Campbell ML: Expression of the proto-oncogene Bcl-2 in the prostate and association with emergence of androgen-independent prostate cancer. Cancer Res 52: 6940-6944, 1992

    PubMed  Google Scholar 

  34. Colombel M, Symmans F, Gil S, O'Toole KM, Chopin D, Benson M, Olsson CA, Korsmeyer S, Buttyan R: Detection of the apoptosis-suppressing oncoprotein bcl-2 in hormone-refractory human prostate cancers. Am J Pathol 143: 390-400, 1993

    PubMed  Google Scholar 

  35. Lu QL, Abel P, Foster CS, and Lalani EN: Bcl-2: role in epithelial differentiation and oncogenesis. HumanPathol 27: 102-10, 1996

    Google Scholar 

  36. Stattin P, Damber JE, Karlberg L, Nordgren H, Bergh A: Bcl-2 immunoreactivity in prostate tumorigenesis in relation to prostatic intraepithelial neoplasia, grade, hormonal status, metastatic growth and survival. Urol Res 24: 257-264, 1996

    Article  PubMed  Google Scholar 

  37. Raffo AJ, Perlman H, Chen MW, Day ML, Streitman JS, Buttyan R: Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitroand confers resistance to androgen depletion in vivo. Cancer Res 55: 4438-45, 1995

    PubMed  Google Scholar 

  38. Meeker AK, Sommerfeld HJ, Coffey DS: Telomerase is activated in the prostate and seminal vesicles of the castrated rat. Endocrinology 137: 5743-6, 1996

    Article  PubMed  Google Scholar 

  39. Sommerfield HJ, Meeker AK, Piatyszek MA, Bova GS, Shay JW, Coffey DS: Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res 56: 218-223, 1996

    PubMed  Google Scholar 

  40. Chung LW: The role of stromal-epithelial interaction in normal and malignant growth. Cancer Surveys 23: 33-42, 1995

    PubMed  Google Scholar 

  41. Dorkin TJ, Neal DE: Basic science aspects of prostate cancer. Sem Canc Biol 8: 21-7, 1997

    Article  Google Scholar 

  42. Lyne JC, Melhem MF, Finley GG, Wen D, Liu N, Deng DH, Salup R: Tissue expression of neu differentiation factor/heregulin and its receptor complex in prostate cancer and its biologic effects on prostate cancer cells in vitro. Cancer J Sci Am 3: 21-30, 1997

    PubMed  Google Scholar 

  43. Pisters LL, Troncoso P, Zhau HE, Li W, von Eschenback AC, Chung L: c-met protooncogene expression in benign and malignant human prostate tissues. J Urol 154: 293-298, 1995

    Article  PubMed  Google Scholar 

  44. Culig Z, Hobisch A, Cronauer MV, Radmayr C, Trapman J, Hittmair A, Bartsch G, Klocker H: Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Res 54: 5474-8, 1994

    PubMed  Google Scholar 

  45. Pietrzkowski Z, Wernicke D, Porcu P, Jameson BA, Baserga R: Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1. Cancer Res 52: 6447-51, 1992

    PubMed  Google Scholar 

  46. Myers RB, Grizzle WE: Changes in biomarker expression in the development of prostatic adenocarcinoma. Biotech Histochem 72: 86-95, 1997

    PubMed  Google Scholar 

  47. De Marzo MA, Meeker AK, Epstein JI, Coffey DS: Prostate stem cell compartments: expression of the cell cycle inhibitor p27Kip1 in normal, hyperplastic, and neoplastic cells. Am J Pathol 153: 911-9, 1998

    PubMed  Google Scholar 

  48. Reiter RE, Magi-Galuzzi C, Hemmatti H, Sawyers C, Loda M, Witte ON: Two genes upregulated in androgen-independent prostate cancer are also selectively expressed in the basal cells of normal prostate epithelium. J Urol 157 (Supplement): 269A, 1997

    Google Scholar 

  49. Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E, Wahl M, Nisitani S, Yamashiro J, LeBM, Loda M, WitteON: Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci USA 95: 1735-40, 1998

    Article  PubMed  Google Scholar 

  50. Myers RB, Srivastava S, Oelschlager DK, Grizzle WE: Expression of p160erbB-3 and p185erbB-2 in prostatic intraepithelial neoplasia and prostatic adenocarcinoma (see comments). J Natl Cancer Inst 86: 1140-5, 1994

    PubMed  Google Scholar 

  51. Yang Y, Hao J, Liu X, Dalkin B, Nagle RB: Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma. Am J Pathol 150: 693-704, 1997

    PubMed  Google Scholar 

  52. McNeal JE, Haillot O, Yemoto C: Cell proliferation in dysplasia of the prostate: analysis by PCNA immunostaining. Prostate 27: 258-68, 1995

    PubMed  Google Scholar 

  53. Magi GC, Xu X, Hlatky L, Hahnfeldt P, Kaplan I, Hsiao P, Chang C, Loda M: Heterogeneity of androgen receptor content in advanced prostate cancer. Modern Pathology 10: 839-45, 1997

    PubMed  Google Scholar 

  54. Kadkol SS, Brody JR, Epstein JI, Kuhajda FP, Pasternack GR: Novel nuclear phosphoprotein pp32 is highly expressed in intermediate-and high-grade prostate cancer. Prostate 34: 231-7, 1998

    Article  PubMed  Google Scholar 

  55. Bonkhoff H: Neuroendocrine cells in benign and malignant prostate tissue: morphogenesis, proliferation, and androgen receptor status. Prostate (Supplement) 8: 18-22, 1998

    Article  Google Scholar 

  56. Abrahamsson PA: Neuroendocrine differentiation and hormone-refractory prostate cancer. Prostate (Supplement) 6: 3-8, 1996

    Google Scholar 

  57. di SAP: Neuroendocrine differentiation in carcinoma of the prostate. Diagnostic, prognostic, and therapeutic implications. Cancer, 1992

  58. Jiborn T, Bjartell A, Abrahamsson PA: Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology 51: 585-9, 1998

    Article  PubMed  Google Scholar 

  59. Antica M, Wu L, Scollay R: Stem cell antigen 2 expression in adult and developing mice. Immunology letters 55: 47-51, 1997

    Article  PubMed  Google Scholar 

  60. Classon BJ, Cloverdale L: Mouse stem cell antigen Sca-2 is a member of the Ly-6 family of cell surface proteins. Proc Nat Ac Sci 91: 5296-5300, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, USA

    Matthew Bui & Robert E. Reiter

Authors
  1. Matthew Bui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert E. Reiter
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bui, M., Reiter, R.E. Stem Cell Genes in Androgen-independent Prostate Cancer. Cancer Metastasis Rev 17, 391–399 (1998). https://doi.org/10.1023/A:1006197923640

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1006197923640

Search

Navigation