Advertisement

Characterization of Androgen Regulation of ZEB-1 and PSA in 22RV1 Prostate Cancer Cells

  • Bynthia M. Anose
  • Lisa LaGoo
  • Jamie Schwendinger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

Two-thirds of patients who present with metastatic prostate cancer (PC) are dead within 5 years of diagnosis. The comparable survival rate for patients with localized disease is 100%, which clearly stresses the need for pursuing and developing bioassays that allow prediction of which localized cases are most likely to metastasize. The commonly assayed prostate specific antigen (PSA), while touted as a transformation biomarker, has recently proven to be problematic in the area of false positive diagnoses. It remains, however, a hallmark gene for studying androgen regulation as its expression is reliably stimulated by androgens such as dihydrotestosterone (DHT). Herein, we have elucidated the effects of flutamide (a defined anti-androgen) and DHT on the expression of PSA and Zinc finger E-box Binding factor (ZEB-1). Additionally, we assayed the androgenic capabilities of two DHT derivatives on expression of PSA. Our previous research had identified ZEB-1 as a putative biomarker for the onset of metastasis in prostate cancer. The expression of this gene is regulated by androgen and decreases sharply at metastasis. In the current study, the effects of 1 and 10nM flutamide, in combination with 1 and 10nM DHT, on expression of ZEB-1 and PSA, were investigated in 22Rv1, an androgen-responsive human PC cell line. Also in this cell line, the effects of testosterone propionate and dehydroisoandrosterone were studied. Our research confirmed the feasibility of considering ZEB-1 a metastatic PCa biomarker, using the highly sensitive technique of real-time polymerase chain reaction (RT-PCR). Interestingly, it also revealed the danger of using flutamide as a therapeutic antagonist, as we demonstrate herein its alarming capability to behave as an agonist.

Keywords

Prostate Cancer Testosterone Propi Testosterone Propionate 22Rv1 Cell Androgen Regulation 
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.
    What are the key statistics about prostate cancer? (2006) American Cancer Society, Inc. Accessed 12 May, 2006. Available at http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_prostate_cancer_36.asp?sitearea
  2. 2.
    Hartel A, Didier A, Pfaffl MW, et al. (2003) Characterisation of gene expression patterns in 22RV1 cells for determination of environmental androgenic/antiandrogenic compounds. J Steroid Biochem Mol Biol 84:231–238.PubMedCrossRefGoogle Scholar
  3. 3.
    Barry MJ (2001) Prostate specific antigen testing for early diagnosis of prostate cancer. New Engl J Medicine 344:1373–1377.CrossRefGoogle Scholar
  4. 4.
    Anose BM, Landry MM, and Sanders MM (2004) Investigating the Role and Regulation of ZEB-1 by Quantitative Real-Time PCR. 12th International Congress of Endocrinology, pp. 1473–1478.Google Scholar
  5. 5.
    Ornstein DK, Rao GS, Johnson B, et al. (1996) Combined finasteride and flutamide therapy in men with advanced prostate cancer. Urology 48:901–905.PubMedCrossRefGoogle Scholar
  6. 6.
    Stone NN, Clejan SJ (1991) Response of prostate volume, prostate-specific antigen, and testosterone to flutamide in men with benign prostatic hyperplasia. J Andrology 12:376–380.Google Scholar
  7. 7.
    Airhart RA, Barnett TF, Sullivan JW, et al. (1978) Flutamide therapy for carcinoma of the prostate. S Med J 71:798–801.Google Scholar
  8. 8.
    Taplin ME, Bubley GJ, Shuster TD, et al. (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. New Engl J Med 332:1393–1398.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Bynthia M. Anose
    • 1
  • Lisa LaGoo
  • Jamie Schwendinger
  1. 1.Bethel UniversitySt. PaulUSA

Personalised recommendations