Androgens, lipogenesis and prostate cancer

J Steroid Biochem Mol Biol. 2004 Nov;92(4):273-9. doi: 10.1016/j.jsbmb.2004.10.013. Epub 2004 Dec 19.

Abstract

Both experimental and epidemiological data indicate that androgens are among the main factors controlling the development, maintenance and progression of prostate cancer. Identifying the genes that are regulated by androgens represents a major step towards the elucidation of the mechanisms underlying the impact of androgens on prostate cancer cell biology and is an attractive approach to find novel targets for prostate cancer therapy. Among the genes that have been identified thus far, several genes encode lipogenic enzymes. Studies aimed at the elucidation of the mechanisms underlying androgen regulation of lipogenic genes revealed that androgens coordinately stimulate the expression of these genes through interference with the molecular mechanism controlling activation of sterol regulatory element-binding proteins (SREBPs), lipogenic transcription factors governing cellular lipid homeostasis. The resulting increase in lipogenesis serves the synthesis of key membrane components (phospholipids, cholesterol) and is a major hallmark of cancer cells. Pharmacologic inhibition of lipogenesis or RNA-interference-mediated down-regulation of key lipogenic genes induces apoptosis in cancer cell lines and reduces tumor growth in xenograft models. While increased lipogenesis is already found in the earliest stages of cancer development (PIN) and initially is androgen-responsive it persists or re-emerges with the development of androgen-independent cancer, indicating that lipogenesis is a fundamental aspect of prostate cancer cell biology and is a potential target for chemoprevention and for antineoplastic therapy in advanced prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Androgens / physiology*
  • CCAAT-Enhancer-Binding Proteins / physiology
  • Cerulenin / therapeutic use
  • Cholesterol / physiology
  • DNA-Binding Proteins / physiology
  • Fatty Acid Synthases / antagonists & inhibitors
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lipid Metabolism
  • Lipids / biosynthesis*
  • Male
  • Membrane Proteins / physiology
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Signal Transduction / physiology
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors / physiology

Substances

  • Androgens
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Lipids
  • Membrane Proteins
  • SREBF1 protein, human
  • SREBF2 protein, human
  • SREBP cleavage-activating protein
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors
  • Cerulenin
  • Cholesterol
  • Fatty Acid Synthases