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Androgen Action and Modulation of Prostate and Prostate Cancer Growth: An Historical Perspective

  • Shutsung Liao
  • John M. Kokontis
  • Chih-Pin Chuu
  • Richard A. Hiipakka
Chapter

Abstract

Early models of steroid hormone action emphasized potential effects of these hormones on metabolic pathways to explain their effects on cells. However these models were abandoned soon after the discovery of the pathway for information transfer from DNA to protein through RNA. Testosterone (T), the major circulating androgen in blood, increases mRNA levels in target tissues and is metabolized to 5α-dihydrotestosterone (DHT) by 5α-reducatse in many target organs. DHT is selectively retained as a protein complex, the androgen receptor (AR), in nuclei, the site of RNA synthesis. Metabolism of T to DHT is critical for androgen action in certain tissues based on the phenotype of individuals with mutations in the gene for 5α-reductase. The cloning of the cDNA for AR has revealed its primary structure and its similarity to other steroid receptors, all members of a superfamily of transcription factors controlled by small lipophilic molecules. Various mutations in the gene for AR are responsible for androgen-insensitivity in men and a potential cause of prostate cancer progression. Certain natural products, like the polyunsaturated fatty acid, γ-linoleic acid and the green tea catechin, epigallocatechin gallate (EGCG) are inhibitors of 5α-reductase and may be useful for treatment of disorders dependent on DHT. EGCG also affects appetite and may have a role in the treatment of obesity.

Clinical prostate cancer progression can be mimicked in vitro using the LNCaP human prostate cancer cell line. These cells become hypersensitive to androgens, elevate expression of AR and are repressed by physiological doses of androgens after long-term androgen deprivation or treatment with the antiandrogen, Casodex.

Although androgen receptor signaling is important for prostate cancer growth and progression, and a target of current therapies, other nuclear receptor signaling pathways may have utility in the treatment of prostate cancer. Activation of liver X receptor signaling modulates the growth and progression in human prostate tumor xenografts.

Keywords

Prostate Cancer Androgen Receptor LNCaP Cell Androgen Receptor Expression Prostate Cancer Progression 
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.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Shutsung Liao
    • 1
  • John M. Kokontis
  • Chih-Pin Chuu
  • Richard A. Hiipakka
  1. 1.The Ben May Department for Cancer ResearchThe University of ChicagoThe Gordon Center for Integrative ScienceChicagoUSA

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