Advertisement

Progression of LNCaP Human Prostate Carcinoma Cells: Androgen Receptor Activity and c-myc Gene Expression

  • John M. Kokontis
  • Nissim Hay
  • Richard A. Hiipakka
  • Shutsung Liao
Conference paper

Abstract

Prostatic carcinogenesis is a multi-step process involving progression from precancerous cells to cells that uncontrollably proliferate and metastasize. Understanding the molecular events driving the progression is critical to the early detection of and choice of treatment for prostate cancer. The growth and development of prostate cancer appears to be initially androgen-dependent, making it vulnerable to androgen ablation and anti-androgen therapies (1). However, prostate cancer cells gradually lose androgen dependency, and tumor cells which are resistant to endocrine therapy ultimately proliferate. While loss of androgen receptor (AR) expression may accompany loss of androgen dependency and responsiveness (2), other prerequisite cellular events may occur which allow cell proliferation to bypass the androgen requirement. Loss of AR expression may either drive the selection for such events or occur secondarily (3).

Keywords

Androgen Receptor LNCaP Cell Androgen Receptor Expression Prostate Tumor Cell Androgen Receptor Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Huggins C, Hodges CV (1941) Studies on prostate cancer. I. The effect of castration, of androgen, and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293–297.Google Scholar
  2. 2.
    Quarmby VE, Beckman JWC, Cooke DB (1990) Expression and localization of androgen receptor in the R-3327 Dunning rat prostatic adenocarcinoma. Cancer Res 50:735–739.PubMedGoogle Scholar
  3. 3.
    Darbre PD, King RJB (1987) Progression to steroid insensitivity can occur irrespective of the presence of functional steroid receptors. Cell 51:521–528.PubMedCrossRefGoogle Scholar
  4. 4.
    Kokontis J, Takakura K, Hay N, Liao S (1994) Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long term androgen deprivation. Cancer Res 54: 1566–1573.PubMedGoogle Scholar
  5. 5.
    Horoszewicz JS, Leong SS, Kawinski E (1983) LNCaP model of human prostatic carcinoma. Cancer Res 43:1809–1818.PubMedGoogle Scholar
  6. 6.
    Veldscholte J, Ris-Stalpers C, Kuiper GGJM (1990) 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 Res Comm 173:534–540.PubMedCrossRefGoogle Scholar
  7. 7.
    Kokontis J, Ito K, Hiipakka RA, Liao S (1991) Expression and function of normal and LNCaP androgen receptors in androgen-insensitive human prostatic cancer cells: Altered hormone and antihormone specificity in gene transactivation. Receptor 1:271–279.PubMedGoogle Scholar
  8. 8.
    Wilding G, Chen M, Gelman EP (1989) Aberrant response in vitro of hormone-responsive prostate cancer cells to anti-androgens. Prostate 14:103–115.PubMedCrossRefGoogle Scholar
  9. 9.
    Olea N, Sakabe K, Soto AM, Sonnenscheim C (1990) The proliferative effect of “anti-androgens” on the androgen-sensitive human prostate tumor cell line LNCAP. Endocrinology 126:1457–1463.PubMedCrossRefGoogle Scholar
  10. 10.
    Isaacs JT, Coffey DS (1981) Adaptation versus selection on the mechanism responsible for the relapse of prostate cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res 41:5070–5075.PubMedGoogle Scholar
  11. 11.
    Wolf DA, Schulz P, Fittier F (1991) Synthetic androgens suppress the transformed phenotype in the human prostate carcinoma cell line LNCaP. Brit J Cancer 64:47–53.PubMedCrossRefGoogle Scholar
  12. 12.
    Parker MG, Webb P, Needham M, et al. (1987) Identification of androgen response elements in mouse mammary tumour virus and the rat prostate C3 gene. J Cell Biochem 35:285–292.PubMedCrossRefGoogle Scholar
  13. 13.
    Riegman PHJ, Vietstra RJ, Van der Korput JAGM (1991) The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol Endocrin 5:1921–1930.CrossRefGoogle Scholar
  14. 14.
    Liao S, Kokontis J, Sai T, Hiipakka RA (1989) Androgen receptors: Structures, mutations, antibodies and cellular dynamics. J Steroid Biochem Mol Biol 34:41–5651.Google Scholar
  15. 15.
    Rubin SJ, Hallahan DE, Ashman CR (1991) Two prostate carcinoma cell lines demonstrate abnormalities in tumor suppressor genes. J Surg Oncol 46:31–36.PubMedCrossRefGoogle Scholar
  16. 16.
    Bookstein R, Shew JY, Chen PL (1990) Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247:712–715PubMedCrossRefGoogle Scholar
  17. 17.
    Egawa S, Kadmon D, Miller GJ (1992) Alterations in mRNA levels for growth-related genes after transplantation into castrated hosts in oncogene-induced clonal mouse prostate carcinoma. Mol Carcinogen 5:52–61.CrossRefGoogle Scholar
  18. 18.
    Connolly JM, Rose DP (1990) Production of epidermal growth factor and transforming growth factor-alpha by the androgen-responsive LNCaP human prostate cancer cell line. Prostate 16:209–218.PubMedCrossRefGoogle Scholar
  19. 19.
    Wilding G, Valverius E, Knabbe C, Gelmann, EP (1989) Role of transforming growth factor-a in human prostate cancer cell growth. Prostate 15:1–12.PubMedCrossRefGoogle Scholar
  20. 20.
    Schuurmans ALG, Bolt J, Voorhorst MM (1988) Regulation of growth and epidermal growth factor receptor levels of LNCaP prostate tumor cells by different steroids. Int J Cancer 42:917–922.Google Scholar
  21. 21.
    Eaton CL, Davies P, Phillips MEA (1988) Growth factor involvement and oncogene expression in prostatic tumours. J Steroid Biochem 30:341–345.PubMedCrossRefGoogle Scholar
  22. 22.
    Ran W, Dean M, Levine RA (1986) Induction of c-fos and c-myc mRNA by epidermal growth factor or calcium ionophore is cAMP dependent. Proc Natl Acad Sci USA 83:8216–8220.PubMedCrossRefGoogle Scholar
  23. 23.
    Fleming WH, Hamel A, MacDonald R (1986) Expression of the c-myc proto-oncogene in human prostatic carcinoma and benign prostatic hyperplasia. Cancer Res 46:1526–1531.Google Scholar
  24. 24.
    Buttyan R, Sawchuk IS, Benson, MC (1987) Enhanced expression of the c-myc protooncogene in high-grade human prostate cancers. Prostate 11:327–337.PubMedCrossRefGoogle Scholar
  25. 25.
    Thompson TC, Southgate J, Kitchener G, Land H (1989) Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ. Cell 56:917–930.PubMedCrossRefGoogle Scholar
  26. 26.
    Quarmby VE, Beckman J W C, M WE, French FS (1987) Androgen regulation of c-myc messenger ribonucleic acid levels in rat ventral prostate. Mol Endocrinol 1:865–874.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1996

Authors and Affiliations

  • John M. Kokontis
  • Nissim Hay
  • Richard A. Hiipakka
  • Shutsung Liao

There are no affiliations available

Personalised recommendations