Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells, with increased sensitivity to whole body gamma-radiation. Export

@article{citeulike:1318238, abstract = {Caveolin-1 (Cav-1) is a protein marker for caveolae organelles, and acts as a scaffolding protein to negatively regulate the activity of signaling molecules by binding to and releasing them in a timely fashion. We have previously shown that loss of Cav-1 promotes the proliferation of mouse embryo fibroblasts (MEFs) in vitro. Here, to investigate the in vivo relevance of these findings, we evaluated the turnover rates of small intestine crypt stem cells from WT and Cav-1 deficient mice. Interestingly, we show that Cav-1 null crypt stem cells display higher proliferation rates, as judged by BrdU and PCNA staining. In addition, we show that Wnt/beta-catenin signaling, which normally controls intestinal stem cell self-renewal, is up-regulated in Cav-1 deficient crypt stem cells. Because the small intestine constitutes one of the main targets of radiation, we next evaluated the role of Cav-1 in radiation-induced damage. Interestingly, after exposure to 15 Gy of gamma-radiation, Cav-1 deficient mice displayed a decreased survival rate, as compared to WT mice. Our results show that after radiation treatment, Cav-1 null crypt stem cells of the small intestine exhibit far more apoptosis and accelerated proliferation, leading to a faster depletion of crypts and villi. As a consequence, six days after radiation treatment, Cav-1(-/-) mice lost all their crypt and villus structures, while WT mice still showed some crypts and intact villi. In summary, we show that ablation of Cav-1 gene expression induces an abnormal amplification of crypt stem cells, resulting in increased susceptibility to gamma-radiation. Thus, our studies provide the first evidence that Cav-1 normally regulates the proliferation of intestinal stem cells in vivo.}, address = {Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.}, author = {Li, J. and Hassan, G. S. and Williams, T. M. and Minetti, C. and Pestell, R. G. and Tanowitz, H. B. and Frank, P. G. and Sotgia, F. and Lisanti, M. P.}, citeulike-article-id = {1318238}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/16294037}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=16294037}, issn = {1551-4005}, journal = {Cell Cycle}, keywords = {apoptosis, caveolin-1, in\_vivo, intestine, mice, proliferation, radiation, stem\_cell}, month = {December}, number = {12}, pages = {1817--1825}, posted-at = {2007-05-21 21:46:35}, priority = {2}, title = {Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells, with increased sensitivity to whole body gamma-radiation.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16294037}, volume = {4}, year = {2005} }

TY - JOUR ID - citeulike:1318238 L3 - citeulike-article-id:1318238 N2 - Caveolin-1 (Cav-1) is a protein marker for caveolae organelles, and acts as a scaffolding protein to negatively regulate the activity of signaling molecules by binding to and releasing them in a timely fashion. We have previously shown that loss of Cav-1 promotes the proliferation of mouse embryo fibroblasts (MEFs) in vitro. Here, to investigate the in vivo relevance of these findings, we evaluated the turnover rates of small intestine crypt stem cells from WT and Cav-1 deficient mice. Interestingly, we show that Cav-1 null crypt stem cells display higher proliferation rates, as judged by BrdU and PCNA staining. In addition, we show that Wnt/beta-catenin signaling, which normally controls intestinal stem cell self-renewal, is up-regulated in Cav-1 deficient crypt stem cells. Because the small intestine constitutes one of the main targets of radiation, we next evaluated the role of Cav-1 in radiation-induced damage. Interestingly, after exposure to 15 Gy of gamma-radiation, Cav-1 deficient mice displayed a decreased survival rate, as compared to WT mice. Our results show that after radiation treatment, Cav-1 null crypt stem cells of the small intestine exhibit far more apoptosis and accelerated proliferation, leading to a faster depletion of crypts and villi. As a consequence, six days after radiation treatment, Cav-1(-/-) mice lost all their crypt and villus structures, while WT mice still showed some crypts and intact villi. In summary, we show that ablation of Cav-1 gene expression induces an abnormal amplification of crypt stem cells, resulting in increased susceptibility to gamma-radiation. Thus, our studies provide the first evidence that Cav-1 normally regulates the proliferation of intestinal stem cells in vivo. IS - 12 JF - Cell Cycle SN - 1551-4005 AD - Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. EP - 1825 TI - Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells, with increased sensitivity to whole body gamma-radiation. VL - 4 SP - 1817 KW - apoptosis KW - caveolin-1 KW - in_vivo KW - intestine KW - mice KW - proliferation KW - radiation KW - stem_cell AU - Li, J AU - Hassan, GS AU - Williams, TM AU - Minetti, C AU - Pestell, RG AU - Tanowitz, HB AU - Frank, PG AU - Sotgia, F AU - Lisanti, MP PY - 2005/12// UR - http://view.ncbi.nlm.nih.gov/pubmed/16294037 ER -