HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kottke, T. J. Articles by Kaufmann, S. H. Search for Related Content PubMed PubMed Citation Articles by Kottke, T. J. Articles by Kaufmann, S. H. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 22, 15927-15936, May 28, 1999

Comparison of Paclitaxel-, 5-Fluoro-2'-deoxyuridine-, and Epidermal Growth Factor (EGF)-induced Apoptosis
EVIDENCE FOR EGF-INDUCED ANOIKIS

Timothy J. Kottke, April L. Blajeski, L. Miguel Martins^§, Peter W. Mesner Jr., Nancy E. Davidson, William C. Earnshaw^§, Deborah K. Armstrong, and Scott H. Kaufmann

From the Division of Oncology Research, Mayo Clinic and the  Department of Pharmacology, Mayo Graduate School, Rochester, Minnesota 55905, the ^§ Institute of Cell & Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom, and the  Johns Hopkins Oncology Center, Baltimore, Maryland 21287

Epidermal growth factor (EGF), a hormone that stimulates proliferation of many cell types, induces apoptosis in some cell lines that overexpress the EGF receptor. To evaluate the mechanism of EGF-induced apoptosis, MDA-MB-468 breast cancer cells were examined by microscopy, flow cytometry, immunoblotting, enzyme assays, and affinity labeling after treatment with EGF, paclitaxel, or 5-fluoro-2'-deoxyuridine (5FUdR). Apoptosis induced by all three agents was accompanied by activation of caspases-3, -6, and -7, as indicated by disappearance of the corresponding zymogens from immunoblots, cleavage of substrate polypeptides in situ, and detection of active forms of these caspases in cytosol and nuclei using fluorogenic assays and affinity labeling. Further analysis indicated involvement of the cytochrome c/Apaf-1/caspase-9 pathway of caspase activation, but not the Fas/Fas ligand pathway. Interestingly, caspase activation was consistently lower after EGF treatment than after paclitaxel or 5FUdR treatment. Additional experiments revealed that the majority of cells detaching from the substratum after EGF (but not paclitaxel or 5FUdR) were morphologically normal and retained the capacity to readhere, suggesting that EGF-induced apoptosis involves cell detachment followed by anoikis. These observations not only indicate that EGF- and chemotherapy-induced apoptosis in this cell line involve the same downstream pathways but also suggest that detachment-induced apoptosis is responsible for the paradoxical antiproliferative effects of EGF.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				K. Rafiq, M. Hanscom, K. Valerie, S. F. Steinberg, and A. Sabri Novel Mode for Neutrophil Protease Cathepsin G Mediated Signaling: Membrane Shedding of Epidermal Growth Factor Is Required for Cardiomyocyte Anoikis Circ. Res., January 4, 2008; 102(1): 32 - 41. [Abstract] [Full Text] [PDF]

				J. Kaganoi, G. Watanabe, M. Okabe, S. Nagatani, A. Kawabe, Y. Shimada, M. Imamura, and Y. Sakai STAT1 Activation-Induced Apoptosis of Esophageal Squamous Cell Carcinoma Cells In Vivo Ann. Surg. Oncol., April 1, 2007; 14(4): 1405 - 1415. [Abstract] [Full Text] [PDF]

				P. Haluska, J. M. Carboni, D. A. Loegering, F. Y. Lee, M. Wittman, M. G. Saulnier, D. B. Frennesson, K. R. Kalli, C. A. Conover, R. M. Attar, et al. In vitro and In vivo Antitumor Effects of the Dual Insulin-Like Growth Factor-I/Insulin Receptor Inhibitor, BMS-554417 Cancer Res., January 1, 2006; 66(1): 362 - 371. [Abstract] [Full Text] [PDF]

				H. A. Erickson, M. D. Jund, and C. A. Pennell Cytotoxicity of human RNase-based immunotoxins requires cytosolic access and resistance to ribonuclease inhibition Protein Eng. Des. Sel., January 1, 2006; 19(1): 37 - 45. [Abstract] [Full Text] [PDF]

				L. M. Howells, E. A. Hudson, and M. M. Manson Inhibition of Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Is Not Sufficient to Account for Indole-3-Carbinol-Induced Apoptosis in Some Breast and Prostate Tumor Cells Clin. Cancer Res., December 1, 2005; 11(23): 8521 - 8527. [Abstract] [Full Text] [PDF]

				M. Kim, K. Murphy, F. Liu, S. E. Parker, M. L. Dowling, W. Baff, and G. D. Kao Caspase-Mediated Specific Cleavage of BubR1 Is a Determinant of Mitotic Progression Mol. Cell. Biol., November 1, 2005; 25(21): 9232 - 9248. [Abstract] [Full Text] [PDF]

				Z. Zhao, D. Garbett, J. L Hill, and D. J Gross Epidermal growth factor receptor downregulation in cultured bovine cumulus cells: reconstitution of calcium signaling and stimulated membrane permeabilization Reproduction, October 1, 2005; 130(4): 517 - 528. [Abstract] [Full Text] [PDF]

				K. A. Lewis, S. Mullany, B. Thomas, J. Chien, R. Loewen, V. Shridhar, and W. A. Cliby Heterozygous ATR Mutations in Mismatch Repair-Deficient Cancer Cells Have Functional Significance Cancer Res., August 15, 2005; 65(16): 7091 - 7095. [Abstract] [Full Text] [PDF]

				J. W. Hong, M. S. Ryu, and I. K. Lim Phosphorylation of Serine 147 of tis21/BTG2/pc3 by p-Erk1/2 Induces Pin-1 Binding in Cytoplasm and Cell Death J. Biol. Chem., June 3, 2005; 280(22): 21256 - 21263. [Abstract] [Full Text] [PDF]

				V. M. Pushkarev, D. V. Starenki, V. A. Saenko, H. Namba, J. Kurebayashi, M. D. Tronko, and S. Yamashita Molecular Mechanisms of the Effects of Low Concentrations of Taxol in Anaplastic Thyroid Cancer Cells Endocrinology, July 1, 2004; 145(7): 3143 - 3152. [Abstract] [Full Text] [PDF]

				D. C. Han, M.-Y. Lee, K. D. Shin, S. B. Jeon, J. M. Kim, K.-H. Son, H.-C. Kim, H.-M. Kim, and B.-M. Kwon 2'-Benzoyloxycinnamaldehyde Induces Apoptosis in Human Carcinoma via Reactive Oxygen Species J. Biol. Chem., February 20, 2004; 279(8): 6911 - 6920. [Abstract] [Full Text] [PDF]

				N. Korfali, S. Ruchaud, D. Loegering, D. Bernard, C. Dingwall, S. H. Kaufmann, and W. C. Earnshaw Caspase-7 Gene Disruption Reveals an Involvement of the Enzyme during the Early Stages of Apoptosis J. Biol. Chem., January 9, 2004; 279(2): 1030 - 1039. [Abstract] [Full Text] [PDF]

				R. J. Anto, M. Venkatraman, and D. Karunagaran Inhibition of NF-{kappa}B Sensitizes A431 Cells to Epidermal Growth Factor-induced Apoptosis, whereas Its Activation by Ectopic Expression of RelA Confers Resistance J. Biol. Chem., July 3, 2003; 278(28): 25490 - 25498. [Abstract] [Full Text] [PDF]

				N. O'Donovan, J. Crown, H. Stunell, A. D. K. Hill, E. McDermott, N. O'Higgins, and M. J. Duffy Caspase 3 in Breast Cancer Clin. Cancer Res., February 1, 2003; 9(2): 738 - 742. [Abstract] [Full Text] [PDF]

				A. A. Habib, S. J. Chun, B. G. Neel, and T. Vartanian Increased Expression of Epidermal Growth Factor Receptor Induces Sequestration of Extracellular Signal-Related Kinases and Selective Attenuation of Specific Epidermal Growth Factor-Mediated Signal Transduction Pathways Mol. Cancer Res., January 1, 2003; 1(3): 219 - 233. [Abstract] [Full Text]

				C. R. Arnt, M. V. Chiorean, M. P. Heldebrant, G. J. Gores, and S. H. Kaufmann Synthetic Smac/DIABLO Peptides Enhance the Effects of Chemotherapeutic Agents by Binding XIAP and cIAP1 in Situ J. Biol. Chem., November 8, 2002; 277(46): 44236 - 44243. [Abstract] [Full Text] [PDF]

				T. J. Kottke, A. L. Blajeski, X. W. Meng, P. A. Svingen, S. Ruchaud, P. W. Mesner Jr., S. A. Boerner, K. Samejima, N. V. Henriquez, T. J. Chilcote, et al. Lack of Correlation between Caspase Activation and Caspase Activity Assays in Paclitaxel-treated MCF-7 Breast Cancer Cells J. Biol. Chem., January 4, 2002; 277(1): 804 - 815. [Abstract] [Full Text]

				C.-P. H. Yang and S. B. Horwitz Taxol Mediates Serine Phosphorylation of the 66-kDa Shc Isoform Cancer Res., September 1, 2000; 60(18): 5171 - 5178. [Abstract] [Full Text]

				P. A. Svingen, A. Tefferi, T. J. Kottke, G. Kaur, V. L. Narayanan, E. A. Sausville, and S. H. Kaufmann Effects of the bcr/abl Kinase Inhibitors AG957 and NSC 680410 on Chronic Myelogenous Leukemia Cells in Vitro Clin. Cancer Res., January 1, 2000; 6(1): 237 - 249. [Abstract] [Full Text]

				N. T. Ueno, C. Bartholomeusz, J. L. Herrmann, Z. Estrov, R. Shao, M. Andreeff, J. Price, R. W. Paul, P. Anklesaria, D. Yu, et al. E1A-mediated Paclitaxel Sensitization in HER-2/neu-overexpressing Ovarian Cancer SKOV3.ip1 through Apoptosis Involving the Caspase-3 Pathway Clin. Cancer Res., January 1, 2000; 6(1): 250 - 259. [Abstract] [Full Text]

				P. W. Mesner Jr., K. C. Bible, L. M. Martins, T. J. Kottke, S. M. Srinivasula, P. A. Svingen, T. J. Chilcote, G. S. Basi, J. S. Tung, S. Krajewski, et al. Characterization of Caspase Processing and Activation in HL-60 Cell Cytosol Under Cell-free Conditions. NUCLEOTIDE REQUIREMENT AND INHIBITOR PROFILE J. Biol. Chem., August 6, 1999; 274(32): 22635 - 22645. [Abstract] [Full Text] [PDF]

				M. Thangaraju, S. H. Kaufmann, and F. J. Couch BRCA1 Facilitates Stress-induced Apoptosis in Breast and Ovarian Cancer Cell Lines J. Biol. Chem., October 20, 2000; 275(43): 33487 - 33496. [Abstract] [Full Text] [PDF]

				W. A. Cliby, K. A. Lewis, K. K. Lilly, and S. H. Kaufmann S Phase and G2 Arrests Induced by Topoisomerase I Poisons Are Dependent on ATR Kinase Function J. Biol. Chem., January 4, 2002; 277(2): 1599 - 1606. [Abstract] [Full Text] [PDF]

				J. Yu, T. F. Deuel, and H.-R. C. Kim Platelet-derived Growth Factor (PDGF) Receptor-alpha Activates c-Jun NH2-terminal Kinase-1 and Antagonizes PDGF Receptor-beta -induced Phenotypic Transformation J. Biol. Chem., June 16, 2000; 275(25): 19076 - 19082. [Abstract] [Full Text] [PDF]