+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin



Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein survivin



Journal of Cell Science 119(Pt 9): 1812-1823



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011835840

Download citation: RISBibTeXText

PMID: 16608879

DOI: 10.1242/jcs.02894


Related references

Expression of survivin and P63 protein in B cell non-Hodgkin's lymphoma and their effects on cell apoptosis and proliferation. Zhongguo Shi Yan Xue Ye Xue Za Zhi 15(1): 99, 2007

Association between survivin expression and cell proliferation in renal cell carcinoma Regulation of survivin by insulin-like growth factor-1, interferon-gamma and a novel NF-kappaB inhibitor dehydroxymethyl-epoxyquinomicin. Journal of Urology 171(4 Suppl.): 202, 2004

Survivin apoptosis: an interloper between cell death and cell proliferation in cancer. Laboratory Investigation; a Journal of Technical Methods and Pathology 79(11): 1327-1333, 1999

Targeting of X-linked inhibitor of apoptosis protein or survivin by short interfering RNAs sensitize hepatoma cells to TNF-related apoptosis-inducing ligand- and chemotherapeutic agent-induced cell death. Oncology Reports 14(5): 1311-1316, 2005

The Anti-Apoptosis Protein Survivin and Cyclin Dependent Kinase Inhibitor P21WAF1/CIP1 Axis Regulate Proliferation of Normal Hematopoietic Progenitors but Survivin Enhances Cell Cycle Independent of P21WAF1/CIP1. Blood 100(11): Abstract No 1166, 2002

Expression of survivin, a novel apoptosis inhibitor and cell cycle regulatory protein, in human gliomas. Chinese Medical Journal 117(4): 612-614, 2004

Expression of survivin, a novel inhibitor of apoptosis and cell cycle regulatory protein, in pancreatic adenocarcinoma. British Journal of Cancer 86(6): 886-892, 2002

Dissection of signals controlling T cell function and activation: H7, an inhibitor of protein kinase C, blocks induction of primary T cell proliferation by suppressing interleukin (IL)2 receptor expression without affecting IL2 production. European Journal of Immunology 21(7): 1575-1582, 1991

Survivin associates with cell proliferation in renal cancer cells: Regulation of survivin expression by insulin-like growth factor-1, interferon-7 and a novel NF-kappa B inhibitor. International Journal of Oncology 28(4): 841-846, 2006

Study on expression of survivin gene and its relations with cell apoptosis and proliferation in nasal NK/T cell lymphoma. Wuhan Daxue Xuebao (Yixue Ban) 25(5): 501-503, 520, 2004

Survivin associates with cell proliferation in renal cancer cells: regulation of survivin expression by insulin-like growth factor-1, interferon-gamma and a novel NF-kappaB inhibitor. International Journal of Oncology 28(4): 841-846, 2006

Expression and significance of apoptosis protein inhibitor survivin and XIAP, in patients with myelodysplastic syndromes and in the cell line MUTZ-1. Zhonghua Xue Ye Xue Za Zhi 25(1): 26-30, 2004

Expression of the inhibitor of apoptosis protein, Survivin, is up regulated in quiescent cord blood CD34+ cells before entry into cell cycle. Experimental Hematology (Charlottesville) 30(6 Suppl. 1): 56, 2002

Targeting Survivin expression induces cell proliferation defect and subsequent cell death involving mitochondrial pathway in myeloid leukemic cells. Cell Cycle 2(5): 488-493, 2003

High nuclear expression of the apoptosis inhibitor protein survivin is associated with disease recurrence and poor prognosis in laryngeal basaloid squamous cell carcinoma. Acta Oto-Laryngologica 126(2): 197-203, 2006