Abstract
Caveolin-1 (cav-1) and the cancer-promoting growth factors vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF-β1), and fibroblast growth factor 2 (FGF2) are often found to be upregulated in advanced prostate cancer and other malignancies. However, the relationship between cav-1 overexpression and growth factor upregulation remains unclear. This report presents, to our knowledge, the first evidence that in prostate cancer cells, a positive autoregulatory feedback loop is established in which VEGF, TGF-β1, and FGF2 upregulate cav-1, and cav-1 expression, in turn, leads to increased levels of VEGF, TGF-β1, and FGF2 mRNA and protein, resulting in enhanced invasive activities of prostate cancer cells, i.e., migration and motility. Our results further show that cav-1–enhanced mRNA stability is a major mechanism underlying the upregulation of these cancer-promoting growth factors, and that PI3-K-Akt signaling is required for forming this positive autoregulatory feedback loop.(Mol Cancer Res 2009;7(11):1781–91)
- caveolin-1
- Akt
- cancer promoting growth factors
- mRNA stability
Footnotes
Grant support: Grant R01-50588 from the National Cancer Institute and by grant PC051247 from the Department of Defense.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/).
- Received June 10, 2009.
- Revision received September 16, 2009.
- Accepted September 24, 2009.
- © 2009 American Association for Cancer Research.
Volume 7, Issue 11
