Prostate cancer (PCa) continues to be one of the leading causes of cancer-related deaths among American men. The prostate relies upon the androgen receptor (AR) to mediate the effects of androgens on normal growth, a reliance that is maintained during malignant prostate growth. Caveolin-1 (Cav-1), the main structural component of caveolae, has been shown to promote the malignant growth and invasion of prostate tumors. In vitro work has shown that Cav-1 can act as an AR coactivator by enhancing its transciptional activity. However, it is unknown how Cav-1 affects androgen-dependent growth and signaling in vivo. To explore this role, a novel mouse model of Cav-1 overexpression was developed with a hormone-insensitive promoter. Cav-1 transgenic (Tg) mice subjected to castration and androgen stimulation display enlarged prostate weights and increased DNA synthesis. Through gene transcript and proteomic profiling, we demonstrate that Cav-1 overexpression favors androgen-regulated responses and enhances processes involved in transcription, cell cycle progression and protein synthesis. Interestingly, Cav-1 overexpression was associated with an increase in the phosphorylation of AR on serine 210, a post-translational modification linked to its activity under androgen-stimulated conditions. In addition, these mice exhibited an increase in the phosphorylation of ribosomal S6 protein on serine 235/236 (pS6), a marker of protein synthesis and a downstream component of the mTOR pathway. Thus, Cav-1 Tg mice could serve as a novel model for studying AR-regulated pathways involved in prostate growth and proliferation. © 2011 Elsevier Ltd. All rights reserved.

Caveolin-1 overexpression enhances androgen-dependent growth and proliferation in the mouse prostate / Kelly G., Bryant; Jeanette, Camacho; Jean Francois, Jasmin; Chenguang, Wang; Sankar, Addya; Mathew C., Casimiro; Fortina, Paolo; Sucharitha, Balasubramaniam; Karen E., Knudsen; Roland, Schwarting; Michael P., Lisanti; Isabelle, Mercier. - In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. - ISSN 1357-2725. - STAMPA. - 43:9(2011), pp. 1318-1329. [10.1016/j.biocel.2011.04.019]

Caveolin-1 overexpression enhances androgen-dependent growth and proliferation in the mouse prostate

FORTINA, PAOLO;
2011

Abstract

Prostate cancer (PCa) continues to be one of the leading causes of cancer-related deaths among American men. The prostate relies upon the androgen receptor (AR) to mediate the effects of androgens on normal growth, a reliance that is maintained during malignant prostate growth. Caveolin-1 (Cav-1), the main structural component of caveolae, has been shown to promote the malignant growth and invasion of prostate tumors. In vitro work has shown that Cav-1 can act as an AR coactivator by enhancing its transciptional activity. However, it is unknown how Cav-1 affects androgen-dependent growth and signaling in vivo. To explore this role, a novel mouse model of Cav-1 overexpression was developed with a hormone-insensitive promoter. Cav-1 transgenic (Tg) mice subjected to castration and androgen stimulation display enlarged prostate weights and increased DNA synthesis. Through gene transcript and proteomic profiling, we demonstrate that Cav-1 overexpression favors androgen-regulated responses and enhances processes involved in transcription, cell cycle progression and protein synthesis. Interestingly, Cav-1 overexpression was associated with an increase in the phosphorylation of AR on serine 210, a post-translational modification linked to its activity under androgen-stimulated conditions. In addition, these mice exhibited an increase in the phosphorylation of ribosomal S6 protein on serine 235/236 (pS6), a marker of protein synthesis and a downstream component of the mTOR pathway. Thus, Cav-1 Tg mice could serve as a novel model for studying AR-regulated pathways involved in prostate growth and proliferation. © 2011 Elsevier Ltd. All rights reserved.
2011
prostate; testosterone; androgen receptor; caveolin-1; mtor; rb
01 Pubblicazione su rivista::01a Articolo in rivista
Caveolin-1 overexpression enhances androgen-dependent growth and proliferation in the mouse prostate / Kelly G., Bryant; Jeanette, Camacho; Jean Francois, Jasmin; Chenguang, Wang; Sankar, Addya; Mathew C., Casimiro; Fortina, Paolo; Sucharitha, Balasubramaniam; Karen E., Knudsen; Roland, Schwarting; Michael P., Lisanti; Isabelle, Mercier. - In: THE INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY. - ISSN 1357-2725. - STAMPA. - 43:9(2011), pp. 1318-1329. [10.1016/j.biocel.2011.04.019]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/377575
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