Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2006) 11 OC6

Signal transduction OC1 Novartis Oncology Young Investigator Award

Activation of androgen membrane binding sites induce potent regression of prostate cancer cells in vitro and in vivo

N Papadopoulou1, M Kampa2, A Gravanis3, E Castanas2 & C Stournaras1


1Department of Biochemistry, University of Crete Medical School, Heraklion, Voutes, Greece; 2Department of Experimental Endocrinology University of Crete Medical School, Heraklion, Voutes, Greece; 3Department of Pharmacology University of Crete Medical School, Heraklion, Voutes, Greece.

Recent data indicate that steroid action can be completed through genomic (late) and non-genomic (rapid) mechanisms. Non-genomic androgen effects are initiated at the membrane level and imply specific secretory and signaling mechanisms different from the classical intracellular androgen receptor activation. In previous work we have reported that androgen membrane binding sites (Ambs) are present in LNCaP human prostate cancer cells. Their activation mediates a FAK/PI3K/Cdc42/Rac1 signaling pathway, resulting in rapid actin cytoskeleton rearrangements and controlling cell proliferation, secretion and motility. In the present study we further evaluated the molecular mechanism of the activation of Ambs and its clinical significance in iAR-expressing (LNCaP) or iAR-negative (DU145) human prostate cancer cells in vitro and in vivo. Here we report that in iAR-negative DU145 cells, activation of Ambs by testosterone-BSA induced a significant actin remodeling followed by the decrease in cell migration, adhesion and invasion. These effects were induced through activation of an alternative pathway involving Rho/ROCK/LIMK2 signaling and leading as well to actin-reorganization. Interestingly, this pathway was not activated in LNCaP cells. Testosterone-BSA induced apoptosis in both LNCaP and DU145 cells, an effect apparently regulated by the actin cytoskeleton reorganization. In addition, in vivo experiments in LNCaP-inoculated nude mice revealed that treatment with testosterone-BSA (8 mg/kg weight) for one month resulted in a 60% reduction of tumor-size, compared to control animals. This effect was not affected by the anti-androgen flutamide. No apparent toxic effects were observed in all treated animals. Our findings suggest that activation of Ambs induce apoptotic regression of prostate cancer cells in vitro and in vivo. Activators of Ambs may represent a new class of antitumoral agents of prostate cancer without apparent side effects.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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