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Acta Physiologica Congress

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Acta Physiologica 2009; Volume 195, Supplement 669
The 88th Annual Meeting of The German Physiological Society
3/22/2009-3/25/2009
Giessen, Germany


COLON TUMORS EXPRESS FUNCTIONAL MEMBRANE ANDROGEN RECEPTORS THAT TRIGGER PRO-APOPTOTIC RESPONSES
Abstract number: P436

Gu1 S., Foller1 M., Anagnostopoulou2 V., Bhavsar1 S., Nasir1 O., Alevizopoulos3 K., Lang1 F., Stournaras1 C.

1Department of Physiology, Eberhard-Karls-University of Tuebingen, Tbingen
2Department of Biochemistry, University of Crete, Heraklion, Greece
3Medexis-Biotech SA Kryoneri Athens, Kryoneri, Greece

Membrane androgen receptors (mARs) have been identified in prostate and breast tumor cells. Their activation was linked to cell growth, motility and apoptosis. Here we report for the first time that mARs are expressed in colonic tumors, CaCo2 and HCT116 colon cancer cell lines. We show that their activation by testosterone albumin conjugates induced (i) effective morphological alterations as indicated by the potent reorganization of actin and tubulin cytoskeleton and (ii) pro-apoptotic responses as documented by annexin V-staining, apo-percentage apoptosis assay and the induction of the activity of the pro-apoptotic executor caspase 3. These effects were observed in the presence of the anti-androgen flutamide. Blockade of mAR-induced actin polymerization by cytochalasin B effectively inhibited the pro-apoptotic responses and caspase 3 activation. We further show that mAR expression is significantly higher in colon tissue specimens of SGK1+/+ compared to SGK1-/- mice, indicating a role of mAR expression in the metastatic potential of colon cancer. In conclusion, our results demonstrate that functional mARs are expressed in colon tumors and their activation by membrane-impermeable testosterone in conjugates results in induction of anti-tumor responses.

To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 669 :P436

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