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Caveolin-1 overexpression enhances androgen-dependent growth and proliferation in the mouse prostate.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2011 Sep; Vol. 43 (9), pp. 1318-29. Date of Electronic Publication: 2011 May 12. - Publication Year :
- 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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Caveolin 1 genetics
Cell Cycle Proteins metabolism
Cell Nucleus metabolism
DNA-Binding Proteins metabolism
Epithelium metabolism
Female
Gene Expression Profiling
Genes, Neoplasm
Male
Mice
Mice, Transgenic
Minichromosome Maintenance Complex Component 7
Nuclear Proteins metabolism
Orchiectomy
Organ Size
Phosphorylation
Prostate cytology
Protein Transport
Proteome genetics
Proteome metabolism
Receptors, Androgen genetics
Receptors, Androgen metabolism
Signal Transduction
TOR Serine-Threonine Kinases metabolism
Testosterone physiology
Transcriptional Activation
Caveolin 1 metabolism
Cell Proliferation
Gene Expression
Prostate growth & development
Testosterone pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 43
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 21601007
- Full Text :
- https://doi.org/10.1016/j.biocel.2011.04.019