title: Androgens, lipogenesis and prostate cancer.
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.
authors.affiliation: Laboratory for Experimental Medicine and Endocrinology, University of Leuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. johan.Swinnen@med.kuleuven.ac.be
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.forename: Hannelore
authors.initials: H
authors.lastname: Heemers
authors.forename: Tine
authors.initials: T
authors.lastname: van de Sande
authors.forename: Ellen
authors.initials: E
authors.lastname: de Schrijver
authors.forename: Koen
authors.initials: K
authors.lastname: Brusselmans
authors.forename: Walter
authors.initials: W
authors.lastname: Heyns
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
mesh_terms: D000728:Androgens / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology; D002569:Cerulenin / Q000627:therapeutic use; D002784:Cholesterol / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000502:physiology
chemical_list: D000728:Androgens; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D002569:Cerulenin; D002784:Cholesterol; D064429:Fatty Acid Synthases