Caveolin-1 Controls Cell Proliferation and Cell Death by Suppressing Expression of the Inhibitor of Apoptosis Protein Survivin.
From: Laboratory of Cellular Communications, FONDAP Center for Molecular Studies of the Cell (CEMC), Facultad de Medicina, Universidad de Chile, Av. Independencia 1027, Santiago, Chile.
Journal of cell science
- Publish Date: May 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 9
- Pages: 1812-23
- Medium: Print
- Language: English
- Citation (JAMA): Torres Vicente A, Tapia Julio C, Rodríguez Diego A, et al. Caveolin-1 Controls Cell Proliferation and Cell Death by Suppressing Expression of the Inhibitor of Apoptosis Protein Survivin.. J. Cell. Sci. May 2006;119:1812-23
Abstract
Caveolin-1 is suggested to act as a tumor suppressor. We tested the hypothesis that caveolin-1 does so by repression of survivin, an Inhibitor of apoptosis protein that regulates cell-cycle progression as well as apoptosis and is commonly overexpressed in human cancers. Ectopic expression of caveolin-1 in HEK293T and ZR75 cells or siRNA-mediated silencing of caveolin-1 in NIH3T3 cells caused downregulation or upregulation of survivin mRNA and protein, respectively. Survivin downregulation in HEK293T cells was paralleled by reduced cell proliferation, increases in G0-G1 and decreases in G2-M phase of the cell cycle. In addition, apoptosis was evident, as judged by several criteria. Importantly, expression of green fluorescent protein-survivin in caveolin-1-transfected HEK293T cells restored cell proliferation and viability. In addition, expression of caveolin-1 inhibited transcriptional activity of a survivin promoter construct in a beta-catenin-Tcf/Lef-dependent manner. Furthermore, in HEK293T cells caveolin-1 associated with beta-catenin and inhibited Tcf/Lef-dependent transcription. Similar results were obtained upon caveolin-1 expression in DLD1 cells, where APC mutation leads to constitutive activation of beta-catenin-Tcf/Lef-mediated transcription of survivin. Taken together, these results suggest that anti-proliferative and pro-apoptotic properties of caveolin-1 may be attributed to reduced survivin expression via a mechanism involving diminished beta-catenin-Tcf/Lef-dependent transcription.
Mesh Headings (Keywords): Animals, Caveolin 1, Cell Cycle, Cell Death, Cell Line, Cell Proliferation, Gene Expression Regulation, Humans, Mice, Microtubule-Associated Proteins, Neoplasm Proteins, RNA, Messenger, Signal Transduction, TCF Transcription Factors, Transcription, Genetic, Wnt Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16608879
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.