|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 32, 29676-29685, August 8, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Insulin-like Growth Factor-binding Protein-5 Inhibits the Growth of Human Breast Cancer Cells in Vitro and in Vivo*
From the Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia
The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell growth is unclear. We determined the effects of IGFBP-5 expression on the growth of human breast cancer cell lines in vivo and in vitro. Expression of IGFBP-5, both by stable transfection and adenoviral-mediated infection, was inhibitory to the growth of MDA-MB-231 and Hs578T human breast cancer cells over a 13-day period. IGFBP-5 expression resulted in a G2/M cell cycle arrest and the induction of apoptosis in both cell lines, an effect that was abrogated in the presence of the broad-spectrum caspase inhibitor, z-VAD-fmk. IGFBP-5-induced apoptosis was associated with a transcriptional increase in expression of the proapoptotic regulator bax and decrease in the anti-apoptotic bcl-2 compared with vector controls. Secreted IGFBP-5 when added exogenously to breast cancer cells was not internalized and had no effect on cell growth or apoptosis, suggesting that IGFBP-5 may elicit its inhibitory effects via a novel, intracrine mechanism. In athymic nude mice, stable expression of IGFBP-5 significantly inhibited both the formation and growth of tumors derived from MDA-MB-231 cells. IGFBP-5-expressing tumors also had a significantly elevated level of bax mRNA and decreased levels of bcl-2 mRNA compared with vector tumors. These data suggest that IGFBP-5 is a potent growth inhibitor and proapoptotic agent in human breast cancer cells via modulation of cell cycle regulation and apoptotic mediators.
Received for publication, February 25, 2003 , and in revised form, May 12, 2003.
* This work was supported by National Health and Medical Research Council, Australia, Grant 107242 (to A. J. B. and R. C. B.). 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.
To whom correspondence should be addressed. Tel.: 61-2-9926-8486; Fax:
61-2-9926-8484; E-mail:
abutt{at}med.usyd.edu.au.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Yakar, C. J. Rosen, M. L. Bouxsein, H. Sun, W. Mejia, Y. Kawashima, Y. Wu, K. Emerton, V. Williams, K. Jepsen, et al. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism FASEB J, March 1, 2009; 23(3): 709 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Rho, S. M. Dong, S. Kang, S.-S. Seo, C. W. Yoo, D. O. Lee, J. S. Woo, and S.-Y. Park Insulin-like growth factor-binding protein-5 (IGFBP-5) acts as a tumor suppressor by inhibiting angiogenesis Carcinogenesis, November 1, 2008; 29(11): 2106 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mukherjee and P. Rotwein Insulin-Like Growth Factor-Binding Protein-5 Inhibits Osteoblast Differentiation and Skeletal Growth by Blocking Insulin-Like Growth Factor Actions Mol. Endocrinol., May 1, 2008; 22(5): 1238 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Mortensen, L. N. Conley, J. Hedegaard, T. Kalstad, P. Sorensen, C. Bendixen, and A. Revhaug Regenerative response in the pig liver remnant varies with the degree of resection and rise in portal pressure Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G819 - G830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mukherjee, E. M. Wilson, and P. Rotwein Insulin-Like Growth Factor (IGF) Binding Protein-5 Blocks Skeletal Muscle Differentiation by Inhibiting IGF Actions Mol. Endocrinol., January 1, 2008; 22(1): 206 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. R. Santer, B. Moser, G. A. Spoden, P. Jansen-Durr, and W. Zwerschke Human papillomavirus type 16 E7 oncoprotein inhibits apoptosis mediated by nuclear insulin-like growth factor-binding protein-3 by enhancing its ubiquitin/proteasome-dependent degradation Carcinogenesis, December 1, 2007; 28(12): 2511 - 2520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Kim, Y. B. Seu, S.-H. Baek, M. J. Kim, K. J. Kim, J. H. Kim, and J.-R. Kim Induction of Cellular Senescence by Insulin-like Growth Factor Binding Protein-5 through a p53-dependent Mechanism Mol. Biol. Cell, November 1, 2007; 18(11): 4543 - 4552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Schedlich, A. Muthukaruppan, M. K. O'Han, and R. C. Baxter Insulin-Like Growth Factor Binding Protein-5 Interacts with the Vitamin D Receptor and Modulates the Vitamin D Response in Osteoblasts Mol. Endocrinol., October 1, 2007; 21(10): 2378 - 2390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Meester-Smoor, A. C Molijn, Y. Zhao, N. A Groen, C. A H Groffen, M. Boogaard, D. van Dalsum-Verbiest, G. C Grosveld, and E. C Zwarthoff The MN1 oncoprotein activates transcription of the IGFBP5 promoter through a CACCC-rich consensus sequence J. Mol. Endocrinol., January 1, 2007; 38(1): 113 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Berfield, K. M. Hansen, and C. K. Abrass Rat glomerular mesangial cells require laminin-9 to migrate in response to insulin-like growth factor binding protein-5 Am J Physiol Cell Physiol, October 1, 2006; 291(4): C589 - C599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Viemann, M. Goebeler, S. Schmid, U. Nordhues, K. Klimmek, C. Sorg, and J. Roth TNF induces distinct gene expression programs in microvascular and macrovascular human endothelial cells J. Leukoc. Biol., July 1, 2006; 80(1): 174 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mazurek, Y. J. Sun, J. E. Price, L. Ramdas, W. Schober, P. Nangia-Makker, J. C. Byrd, A. Raz, and R. S. Bresalier Phosphorylation of Galectin-3 Contributes to Malignant Transformation of Human Epithelial Cells via Modulation of Unique Sets of Genes Cancer Res., December 1, 2005; 65(23): 10767 - 10775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J M Fleming, B J Leibowitz, D E Kerr, and W S Cohick IGF-I differentially regulates IGF-binding protein expression in primary mammary fibroblasts and epithelial cells J. Endocrinol., July 1, 2005; 186(1): 165 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Butt, K. A. Dickson, S. Jambazov, and R. C. Baxter Enhancement of Tumor Necrosis Factor-{alpha}-Induced Growth Inhibition by Insulin-Like Growth Factor-Binding Protein-5 (IGFBP-5), But Not IGFBP-3 in Human Breast Cancer Cells Endocrinology, July 1, 2005; 146(7): 3113 - 3122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yin, R. G. Russell, L. E. Dettin, R. Bai, Z.-L. Wei, A. P. Kozikowski, L. Kopleovich, and R. I. Glazer Peroxisome Proliferator-Activated Receptor {delta} and {gamma} Agonists Differentially Alter Tumor Differentiation and Progression during Mammary Carcinogenesis Cancer Res., May 1, 2005; 65(9): 3950 - 3957. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. M. Salih, S. Mohan, Y. Kasukawa, G. Tripathi, F. A. Lovett, N. F. Anderson, E. J. Carter, J. E. Wergedal, D. J. Baylink, and J. M. Pell Insulin-Like Growth Factor-Binding Protein-5 Induces a Gender-Related Decrease in Bone Mineral Density in Transgenic Mice Endocrinology, February 1, 2005; 146(2): 931 - 940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Eszlinger, K. Krohn, K. Berger, J. Lauter, S. Kropf, M. Beck, D. Fuhrer, and R. Paschke Gene Expression Analysis Reveals Evidence for Increased Expression of Cell Cycle-Associated Genes and Gq-Protein-Protein Kinase C Signaling in Cold Thyroid Nodules J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Spira, J. Beane, V. Pinto-Plata, A. Kadar, G. Liu, V. Shah, B. Celli, and J. S. Brody Gene Expression Profiling of Human Lung Tissue from Smokers with Severe Emphysema Am. J. Respir. Cell Mol. Biol., December 1, 2004; 31(6): 601 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Yin, Q. Xu, and C. Duan Paradoxical Actions of Endogenous and Exogenous Insulin-like Growth Factor-binding Protein-5 Revealed by RNA Interference Analysis J. Biol. Chem., July 30, 2004; 279(31): 32660 - 32666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Dake, M. Boes, L. A. Bach, and R. S. Bar Effect of an Insulin-Like Growth Factor Binding Protein Fusion Protein on Thymidine Incorporation in Neuroblastoma and Rhabdomyosarcoma Cell Lines Endocrinology, July 1, 2004; 145(7): 3369 - 3374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Cobb, D. A. M. Salih, I. Gonzalez, G. Tripathi, E. J. Carter, F. Lovett, C. Holding, and J. M. Pell Partitioning of IGFBP-5 actions in myogenesis: IGF-independent anti-apoptotic function J. Cell Sci., May 1, 2004; 117(9): 1737 - 1746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Butt, J. L. Martin, K. A. Dickson, F. McDougall, S. M. Firth, and R. C. Baxter Insulin-Like Growth Factor Binding Protein-3 Expression Is Associated with Growth Stimulation of T47D Human Breast Cancer Cells: The Role of Altered Epidermal Growth Factor Signaling J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1950 - 1956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. M. Salih, G. Tripathi, C. Holding, T. A. M. Szestak, M. I. Gonzalez, E. J. Carter, L. J. Cobb, J. E. Eisemann, and J. M. Pell Insulin-like growth factor-binding protein 5 (Igfbp5) compromises survival, growth, muscle development, and fertility in mice PNAS, March 23, 2004; 101(12): 4314 - 4319. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |