Urological Research

, Volume 22, Issue 1, pp 33–38 | Cite as

Androgen receptors and hormone sensitivity of a human prostatic cancer cell line (PC-3) are modulated by natural beta-interferon

  • G. Sica
  • G. Dell'Acqua
  • F. Iacopino
  • A. Fattorossi
  • P. Marchetti
  • T. H. van der Kwast
  • M. Pavone-Macaluso
Original Paper


Androgen recptors are expressed at a low level in the cell line PC-3, which does not respond to either androgens or antiandrogens. If these cells are exposed to natural beta-interferon (β-IFN) a reduction in cell growth and an increase in androgen receptors, evaluated by both biochemical and immunocytochemical techniques, occur. This increase seems not to be related to a selective block of PC-3 in any phase of the cell cycle. Pretreatment with β-IFN determines in PC-3 cells a partial responsiveness to the androgen dihydrotestosterone as reflected by the increase in cell number. Moreover, the antiandrogen hydroxyflutamide shows agonistic properties by increasing the cell number of PC-3 cells pre-exposed to β-IFN. When the antiandrogen is tested in combination with interferon, it produces a reduction in the β-IFN-induced inhibition of cell growth. It is not known whether these unexpected effects are due to the increase in androgen receptors or to other mechanisms.

Key words

Androgen receptors Hormone sensitivity Hydroxyflutamide Interferon Prostatic cancer 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cacciatore M, Sica G, Dell'Acqua G, Castagnetta L, Sanfilippo M, Pavone-Macaluso M (1990) Recettori per gli androgeni e risposta alla idrossiflutamide di una linea cellulare stabilizzata di adenocarcinoma prostatico umano. Acta Urol Ital [Suppl] 1:87Google Scholar
  2. 2.
    Carruba G, Pavone C, Pavone-Macaluso M, Mesiti M, d'Aquino A, Vita G, Sica G, Castagnetta L (1989) Morphometry of in vitro systems: an image analysis of two human prostate cancer cell lines (PC-3 and DU-145). Pathol Res Pract 185:704Google Scholar
  3. 3.
    Castagnetta L, Carruba G, Granata OM, Lo Casto M, Arcuri F, Mesiti M, Pavone-Macaluso M (1990) Prostate long-term epithelial cell lines: biological and biochemical features. In: Castagnetta L, d'Aquino S, Labrie F, Bradlow HL (eds) Steroid formation, degradation and action in peripheral tissue. Ann NY Acad Sci 595:149Google Scholar
  4. 4.
    Culig Z, Klocker H, Eberle J, Kaspar F, Hobisch A, Cronauer MV, Bartsch G (1993) DNA sequence of the androgen receptor in prostatic tumor cell lines and tissue specimens assessed by means of the polymerase chain reaction. Prostate 22:11Google Scholar
  5. 5.
    Fentie DD, Lakey WH, McBlain WA (1986) Applicability of nuclear androgen receptor quantification to human prostatic adenocarcinoma, J Urol 135:167Google Scholar
  6. 6.
    Goldstein D, Bushmeyer SM, Witt PL, Jordan VC, Borden EC (1989) Effects of type I and II interferons on cultured human breast cells: interaction with estrogen receptors and with tamoxifen. Cancer Res 49:2698Google Scholar
  7. 7.
    Gonor SE, Lakey WH, McBlain WA (1984) Relationship between concentrations of extractable and matrix-bound nuclear androgen receptor and clinical reponse to endocrine therapy for prostatic adenocarcinoma, J Urol 131:1196Google Scholar
  8. 8.
    Hill AV (1910) The possible effect of the aggregation of the molecule of hemoglobin on its dissociation curve. J Physiol (Lond) 40:4Google Scholar
  9. 9.
    Jakesz R, Smith CA, Aitken S, Huff K, Schuette W, Shackney S, Lippman M (1984) Influence of cell proliferation and cell cycle phase on expression of estrogen receptor in MCF-7 breast cancer cells. Cancer Res 44:619Google Scholar
  10. 10.
    Kaighn ME, Shankar Narayan K, Ohnuki Y, Lechner JF, Jones LW (1979) Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 17:16Google Scholar
  11. 11.
    Kangas L, Nieminen AL, Cantell K (1985) Additive and synergistie effects of a novel antiestrogen, toremifene (Fc-1157a), and human interferons on estrogen responsive MCF-7 cells in vitro. Med Biol 63:187Google Scholar
  12. 12.
    Markaverich BM, Roberts RR, Alejandro MA, Johnson GA, Middleditch BS, Clark JH (1988) Bioflavonoid interaction with rat uterine type II binding sites and cell growth inhibition. J Steroid Biochem 30:71Google Scholar
  13. 13.
    Mobbs BG, Johnson IE, Connolly JG, Thompson J (1983) Concentration and cellular distribution of androgen receptor in human prostatic neoplasia: can estrogen treatment increase androgen receptor content? J Steroid Biochem 19:1279Google Scholar
  14. 14.
    Olea N, Sakabe K, Soto AM, Sonnenschein C (1990) The proliferative effect of “anti-androgens” on the androgen-sensitive human prostate tumor cell line LNCaP. Endocrinology 126:1457Google Scholar
  15. 15.
    Pouillart P, Palangie T, Jouve M, Garcia-Giralt E, Fridman WH, Magdelenat H, Falcoff E, Billiau A (1982) Administration of fibroblast interferon to patients with advanced breast cancer: possible effects on skin metastasis and on hormone recoptors. Eur J Cancer Clin Oncol 18:929Google Scholar
  16. 16.
    Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, Kwast TH van der (1991) Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 39:927Google Scholar
  17. 17.
    Shearer M, Taylor-Papadimitriou J (1987) Regulation of cell growth by interferon. Cancer Metastasis Rev 6:199Google Scholar
  18. 18.
    Sica G, Dell'Acqua G, Pavone-Macaluso M, Cacciatore M, Fabbroni L, Marchetti P (1991) Interferon and hormonesensitivity of prostatic cancer cells. In: Smith PH, Pavone-Macaluso M (eds) EORTC Genitourinary Group monograph 10. Urological oncology: reconstructive surgery, organ conservation, and restoration of function. Wiley-Liss, New York, p 213Google Scholar
  19. 19.
    Sica G, Fabbroni L, Castagnetta L, Cacciatore M, Pavone-Macaluso M (1989) Antiproliferative effect of interferons on human prostate carcinoma cell lines. Urol Res 17:111Google Scholar
  20. 20.
    Sica G, Fabbroni L, Dell'Acqua G, lacopino F, Marchetti P, Cacciatore M, Pavone-Macaluso M (1991) Natural β-interferon and androgen receptors in prostatic cancer cells. Urol Int 46:159Google Scholar
  21. 21.
    Sica G, Natoli V, Stella C, DelBianco S (1987) Effect of natural beta-interferon on cell proliferation and steroid receptor level in human breast cancer cells. Cancer 60:2419Google Scholar
  22. 22.
    Smets LA, Klooster P van der, Otte A (1985) Glucocorticoid receptors of normal and leukemic cells: role of proliferation conditions. Leuk Res 9:199Google Scholar
  23. 23.
    Tilley WD, Wilson CM, Marcelli M, McPhaul MJ (1990) Androgen receptor gene expression in human prostate carcinoma cell lines. Cancer Res 50:5382Google Scholar
  24. 24.
    Turcotte G, Chapdelaine A, Roberts KD, Chevalier S (1988) Androgen binding as evidenced by a whole cell assay system using cultured canine prostatic epithelial cells. J Steroid Biochem 29:69Google Scholar
  25. 25.
    Van den Berg HW, Leahey WJ, Lynch M, Clarke R, Nelson J (1987) Recombinant human interferon alpha increases oestrogen receptor expression in human breast cancer cells (ZR-75-1) and sensitizes them to the anti-proliferative effects of tamoxifen. Br J Cancer 55:255Google Scholar
  26. 26.
    Veldscholte J, Voorhorst-Ogink MM, Bolt-de-Vries J, Rooij HCJ van, Trapman J, Mulder E (1990) Unusual specificity of the androgen receptor in the human prostate tumor cell line LNCaP: high affinity for progestagenic and estrogenic steroids. Biochim Biophys Acta 1052:187Google Scholar
  27. 27.
    Wilding G, Chen M, Gelmann EP (1989) Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens. Prostate 14:103Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • G. Sica
    • 1
  • G. Dell'Acqua
    • 1
  • F. Iacopino
    • 1
  • A. Fattorossi
    • 2
  • P. Marchetti
    • 3
  • T. H. van der Kwast
    • 4
  • M. Pavone-Macaluso
    • 5
  1. 1.Istituto di Istologia ed Embriologia Generale, Facoltà di MedicinaUniversità Cattolica del Sacro CuoreRomeItaly
  2. 2.Laboratotio di ImmunologiaDASRSRomeItaly
  3. 3.Dipartimento di Medicina Sperimentale, Oncologia medicaUniversità degli StudiL'AquilaItaly
  4. 4.Department of PathologyErasmus UniversiteitRotterdamThe Netherlands
  5. 5.Istituto di Clinica UrologicaUniversità di PalermoPalermoItaly

Personalised recommendations