Caveolae contribute to the apoptosis resistance induced by the alpha(1A)-adrenoceptor in androgen-independent prostate cancer cells.
BACKGROUND
During androgen ablation prostate cancer cells' growth and survival become independent of normal regulatory mechanisms. These androgen-independent cells acquire the remarkable ability to adapt to the surrounding microenvironment whose factors, such as neurotransmitters, influence their survival. Although findings are becoming evident about the expression of alpha(1A)-adrenoceptors in prostate cancer epithelial cells, their exact functional role in androgen-independent cells has yet to be established. Previous work has demonstrated that membrane lipid rafts associated with key signalling proteins mediate growth and survival signalling pathways in prostate cancer cells.


RESULTS
In order to analyze the membrane topology of the alpha(1A)-adrenoceptor we explored its presence by a biochemical approach in purified detergent resistant membrane fractions of the androgen-independent prostate cancer cell line DU145. Electron microscopy observations demonstrated the colocalization of the alpha(1A)-adrenoceptor with caveolin-1, the major protein component of caveolae. In addition, we showed that agonist stimulation of the alpha(1A)-adrenoceptor induced resistance to thapsigargin-induced apoptosis and that caveolin-1 was necessary for this process. Further, immunohistofluorescence revealed the relation between high levels of alpha(1A)-adrenoceptor and caveolin-1 expression with advanced stage prostate cancer. We also show by immunoblotting that the TG-induced apoptosis resistance described in DU145 cells is mediated by extracellular signal-regulated kinases (ERK).


CONCLUSIONS
In conclusion, we propose that alpha(1A)-adrenoceptor stimulation in androgen-independent prostate cancer cells via caveolae constitutes one of the mechanisms contributing to their protection from TG-induced apoptosis.
Katsogiannou
Maria
M
Inserm U800, Université Lille 1 Sciences et Technologies, Villeneuve d'Ascq, France.
El Boustany
Charbel
C
Gackiere
Florian
F
Delcourt
Philippe
P
Athias
Anne
A
Mariot
Pascal
P
Dewailly
Etienne
E
Jouy
Nathalie
N
Lamaze
Christophe
C
Bidaux
Gabriel
G
Mauroy
Brigitte
B
Prevarskaya
Natalia
N
Slomianny
Christian
C
D017209:Apoptosis; D021941:Caveolae / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002784:Cholesterol / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D021962:Membrane Microdomains; D008954:Models, Biological; D018377:Neurotransmitter Agents; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D015398:Signal Transduction; D013109:Sphingomyelins / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
C547713:ADRA1A protein, human; D018377:Neurotransmitter Agents; D018340:Receptors, Adrenergic, alpha-1; D013109:Sphingomyelins; D019284:Thapsigargin; D002784:Cholesterol