Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo.
BACKGROUND
Membrane androgen receptors (mAR) have been implicated in the regulation of cell growth, motility and apoptosis in prostate and breast cancer. Here we analyzed mAR expression and function in colon cancer.


RESULTS
Using fluorescent mAR ligands we showed specific membrane staining in colon cell lines and mouse xenograft tumor tissues, while membrane staining was undetectable in healthy mouse colon tissues and non-transformed intestinal cells. Saturation/displacement assays revealed time- and concentration-dependent specific binding for testosterone with a KD of 2.9 nM. Stimulation of colon mAR by testosterone albumin conjugates induced rapid cytoskeleton reorganization and apoptotic responses, even in the presence of anti-androgens. The actin cytoskeleton drug cytochalasin B effectively inhibited the pro-apoptotic responses and caspase-3 activation. Interestingly, in vivo studies revealed that mAR activation resulted in a 65% reduction of tumor incidence in chemically induced Balb/c mice colon tumors.


CONCLUSIONS
Our results demonstrate for the first time that functional mARs are predominantly expressed in colon tumors and that their activation results in induction of anti-tumor responses in vitro and extensive reduction of tumor incidence in vivo.
Gu
Shuchen
S
Department of Physiology, University of Tübingen, Germany. susanuse@googlemail.com
Papadopoulou
Natalia
N
Gehring
Eva-Maria
EM
Nasir
Omaima
O
Dimas
Konstantinos
K
Bhavsar
Shefalee K
SK
Föller
Michael
M
Alevizopoulos
Konstantinos
K
Lang
Florian
F
Stournaras
Christos
C
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D003571:Cytochalasin B / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011944:Receptors, Androgen / Q000502:physiology*
D008565:Membrane Proteins; D011944:Receptors, Androgen; D003571:Cytochalasin B; D053148:Caspase 3