Open AccessCaveolae Contribute to the Apoptosis Resistance Induced by the α1A-Adrenoceptor in Androgen-Independent Prostate Cancer Cells
Author(s) -
Maria Katsogiannou,
Charbel El Boustany,
Florian Gackière,
Philippe Delcourt,
Anne Athias,
Pascal Mariot,
Etienne Dewailly,
Nathalie Jouy,
Christophe Lamaze,
Gabriel Bidaux,
Brigitte Mauroy,
Natalia Prevarskaya,
Christian Slomianny
Publication year - 2009
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0007068
Subject(s) - du145 , prostate cancer , caveolae , microbiology and biotechnology , biology , caveolin 1 , androgen receptor , cancer cell , apoptosis , signal transduction , cancer research , endocrinology , medicine , cancer , lncap , biochemistry , genetics
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 α 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. Methodology/Principal Findings In order to analyze the membrane topology of the α 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 colocalisation of the α 1A -adrenoceptor with caveolin-1, the major protein component of caveolae. In addition, we showed that agonist stimulation of the α 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 α 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/Significance In conclusion, we propose that α 1A -adrenoceptor stimulation in androgen-independent prostate cancer cells via caveolae constitutes one of the mechanisms contributing to their protection from TG-induced apoptosis.