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15 November 2006
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DNA damage elicits a cellular program of damage control coordinated by the kinase activity of ATM. Kirshner et al. show that ATM activity, but not abundance, is severely compromised in murine cells in which the Tgfβ1 gene is deleted and in human epithelial cells in which TGFβ signaling is blocked. This defect is evident by the absence of γH2AX foci at 30 min after exposure to ionizing radiation (2 Gy) in Tgfβ1-null compared to Tgfβ1-heterozygote keratinocytes, as detected by γH2AX immunofluorescence (green) in DAPI-stained nuclei (blue). As a consequence of the failure of ATM to phosphorylate its substrates, inhibiting TGFβ signaling compromises radiation-induced apoptosis and cell-cycle arrest and increases cell kill as measured by clonogenic assay. These data demonstrate a previously unsuspected role for extracellular signaling in the genotoxic stress program of epithelial cells, and contributes a new and important action for TGFβ1 as a tumor suppressor. Future studies to identify the molecular mechanism of ATM kinase inhibition in epithelial cells may support the use of TGFβ inhibitors to increase response to radiotherapy. For details, see the article by Kirshner et al. on page 10861 of this issue.Close Modal - PDF Icon PDF LinkTable of Contents
ISSN 0008-5472
EISSN 1538-7445
Journal Archive
Cancer Research (1941-Present; volumes 1-current)
(ISSN 0008-5472) Published twice monthly since 1987. From 1941-1986, published monthly.The American Journal of Cancer (1931-1940; volumes 15-40)
(ISSN 0099-7374) Published quarterly in 1931, bimonthly in 1932, and monthly from 1933 to 1940. The journal changed title to Cancer Research in 1941.The Journal of Cancer Research (1916-1930); volumes 1-14)
(ISSN 0099-7013) Published quarterly from 1916 through 1930 (publication was suspended from November 1922 to March 1924). The journal changed title to The American Journal of Cancer in 1931.Table of Contents
Reviews
Meeting Report
Priority Reports
Molecular Biology, Pathobiology, and Genetics
Decreased NKX3.1 Protein Expression in Focal Prostatic Atrophy, Prostatic Intraepithelial Neoplasia, and Adenocarcinoma: Association with Gleason Score and Chromosome 8p Deletion
Carlise R. Bethel; Dennis Faith; Xiang Li; Bin Guan; Jessica L. Hicks; Fusheng Lan; Robert B. Jenkins; Charles J. Bieberich; Angelo M. De Marzo
Mutant p53 Protects Cells from 12-O-Tetradecanoylphorbol-13-Acetate–Induced Death by Attenuating Activating Transcription Factor 3 Induction
Yosef Buganim; Eyal Kalo; Ran Brosh; Hila Besserglick; Ido Nachmany; Yoach Rais; Perry Stambolsky; Xiaohu Tang; Michael Milyavsky; Igor Shats; Marina Kalis; Naomi Goldfinger; Varda Rotter
Epigenetic Regulation of Tumor Endothelial Cell Anergy: Silencing of Intercellular Adhesion Molecule-1 by Histone Modifications
Debby M.E.I. Hellebrekers; Karolien Castermans; Emmanuelle Viré; Ruud P.M. Dings; Nicole T.H. Hoebers; Kevin H. Mayo; Mirjam G.A. oude Egbrink; Grietje Molema; François Fuks; Manon van Engeland; Arjan W. Griffioen
Cell, Tumor, and Stem Cell Biology
A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma
Fenghua Liu; Peter J. Park; Weil Lai; Elizabeth Maher; Arnab Chakravarti; Laura Durso; Xiuli Jiang; Yi Yu; Amanda Brosius; Meredith Thomas; Lynda Chin; Cameron Brennan; Ronald A. DePinho; Isaac Kohane; Rona S. Carroll; Peter M. Black; Mark D. Johnson
Reassessment of Id1 Protein Expression in Human Mammary, Prostate, and Bladder Cancers Using a Monospecific Rabbit Monoclonal Anti-Id1 Antibody
Jonathan Perk; Ignacio Gil-Bazo; Yvette Chin; Paola de Candia; John J.S. Chen; Yuntao Zhao; Shirley Chao; Wai Cheong; Yaohuang Ke; Hikmat Al-Ahmadie; William L. Gerald; Edi Brogi; Robert Benezra
Experimental Therapeutics, Molecular Targets, and Chemical Biology
Biological Properties of IDN5174, a New Synthetic Camptothecin with the Open Lactone Ring
Giovanni L. Beretta; Giovanna Petrangolini; Michelandrea De Cesare; Graziella Pratesi; Paola Perego; Stella Tinelli; Monica Tortoreto; Massimo Zucchetti; Roberta Frapolli; Ezia Bello; Carla Manzotti; Gabriele Fontana; Ezio Bombardelli; Arturo Battaglia; Cristian Samorì; Franco Zunino
Immunology
CD28 Costimulation Provided through a CD19-Specific Chimeric Antigen Receptor Enhances In vivo Persistence and Antitumor Efficacy of Adoptively Transferred T Cells
Claudia M. Kowolik; Max S. Topp; Sergio Gonzalez; Timothy Pfeiffer; Simon Olivares; Nancy Gonzalez; David D. Smith; Stephen J. Forman; Michael C. Jensen; Laurence J.N. Cooper
Functional CXCR4-Expressing Microparticles and SDF-1 Correlate with Circulating Acute Myelogenous Leukemia Cells
Alexander Kalinkovich; Sigal Tavor; Abraham Avigdor; Joy Kahn; Alexander Brill; Isabelle Petit; Polina Goichberg; Melania Tesio; Neta Netzer; Elizabeth Naparstek; Izhar Hardan; Arnon Nagler; Igor Resnick; Alexander Tsimanis; Tsvee Lapidot
Endocrinology
Clinical Research
Molecular Imaging of Proliferation in Malignant Lymphoma
Andreas K. Buck; Martin Bommer; Stephan Stilgenbauer; Malik Juweid; Gerhard Glatting; Holger Schirrmeister; Torsten Mattfeldt; Djurdja Tepsic; Donald Bunjes; Felix M. Mottaghy; Bernd J. Krause; Bernd Neumaier; Hartmut Döhner; Peter Möller; Sven N. Reske
Epidemiology and Prevention
DNA Repair and Cell Cycle Control Genes and the Risk of Young-Onset Lung Cancer
Stefano Landi; Federica Gemignani; Federico Canzian; Valérie Gaborieau; Roberto Barale; Debora Landi; Neonilia Szeszenia-Dabrowska; David Zaridze; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Dana Mates; Lenka Foretova; Vladimir Janout; Vladimir Bencko; Lydie Gioia-Patricola; Janet Hall; Paolo Boffetta; Rayjean J. Hung; Paul Brennan
Persistent Human Papillomavirus Infection Is Associated with a Generalized Decrease in Immune Responsiveness in Older Women
Alfonso J. García-Piñeres; Allan Hildesheim; Rolando Herrero; Matthew Trivett; Marcus Williams; Ivannia Atmetlla; Margarita Ramírez; Maricela Villegas; Mark Schiffman; Ana Cecilia Rodríguez; Robert D. Burk; Mariana Hildesheim; Enrique Freer; José Bonilla; Concepción Bratti; Jay A. Berzofsky; Ligia A. Pinto
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