Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 5 February 1988:
Vol. 239. no. 4840, pp. 645 - 647
DOI: 10.1126/science.3277276

Articles

Science, Vol 239, Issue 4840, 645-647
Copyright © 1988 by American Association for the Advancement of Science


articles

The ras oncogenes increase the intrinsic resistance of NIH 3T3 cells to ionizing radiation

MD Sklar

Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor 48109.

Identification of genes that function to protect cells from radiation damage is an essential step in understanding the molecular mechanisms by which mammalian cells cope with ionizing radiation. The intrinsic radiation resistance (D0) of NIH 3T3 cells was markedly and significantly increased by transformation with ras oncogenes activated by missense mutations. This radiobiologic activity appeared to be a specific consequence of the ras mutations rather than of transformation, since revertant cells that contained functional ras genes (but were no longer phenotypically transformed) retained their increased D0's.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
In vitro and In vivo Radiosensitization with AZD6244 (ARRY-142886), an Inhibitor of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase 1/2 Kinase.
E. J. Chung, A. P. Brown, H. Asano, M. Mandler, W. E. Burgan, D. Carter, K. Camphausen, and D. Citrin (2009)
Clin. Cancer Res. 15, 3050-3057
   Abstract »    Full Text »    PDF »
Lapatinib Resistance in HCT116 Cells Is Mediated by Elevated MCL-1 Expression and Decreased BAK Activation and Not by ERBB Receptor Kinase Mutation.
A. P. Martin, A. Miller, L. Emad, M. Rahmani, T. Walker, C. Mitchell, M. P. Hagan, M. A. Park, A. Yacoub, P. B. Fisher, et al. (2008)
Mol. Pharmacol. 74, 807-822
   Abstract »    Full Text »    PDF »
MicroRNAs as Potential Agents to Alter Resistance to Cytotoxic Anticancer Therapy.
J. B. Weidhaas, I. Babar, S. M. Nallur, P. Trang, S. Roush, M. Boehm, E. Gillespie, and F. J. Slack (2007)
Cancer Res. 67, 11111-11116
   Abstract »    Full Text »    PDF »
Stimulated PI3K-AKT Signaling Mediated through Ligand or Radiation-Induced EGFR Depends Indirectly, but not Directly, on Constitutive K-Ras Activity.
M. Toulany, M. Baumann, and H. P. Rodemann (2007)
Mol. Cancer Res. 5, 863-872
   Abstract »    Full Text »    PDF »
Radiotherapy-induced signal transduction.
A. Yacoub, A. Miller, R. W Caron, L. Qiao, D. A Curiel, P. B Fisher, M. P Hagan, S. Grant, and P. Dent (2006)
Endocr. Relat. Cancer 13, S99-S114
   Abstract »    Full Text »    PDF »
A Conserved RAS/Mitogen-Activated Protein Kinase Pathway Regulates DNA Damage-Induced Cell Death Postirradiation in Radelegans.
J. B. Weidhaas, D. M. Eisenmann, J. M. Holub, and S. V. Nallur (2006)
Cancer Res. 66, 10434-10438
   Abstract »    Full Text »    PDF »
HIV Protease Inhibitors Block Akt Signaling and Radiosensitize Tumor Cells Both In vitro and In vivo.
A. K. Gupta, G. J. Cerniglia, R. Mick, W. G. McKenna, and R. J. Muschel (2005)
Cancer Res. 65, 8256-8265
   Abstract »    Full Text »    PDF »
Pancreatic Cancer Cell Radiation Survival and Prenyltransferase Inhibition: The Role of K-Ras.
T. B. Brunner, K. A. Cengel, S. M. Hahn, J. Wu, D. L. Fraker, W. G. McKenna, and E. J. Bernhard (2005)
Cancer Res. 65, 8433-8441
   Abstract »    Full Text »    PDF »
Oncogenic H-Ras Up-regulates Expression of Ku80 to Protect Cells from {gamma}-Ray Irradiation in NIH3T3 Cells.
I.-Y. Chang, C.-K. Youn, H.-B. Kim, M.-H. Kim, H.-J. Cho, Y. Yoon, Y.-S. Lee, M.-H. Chung, and H. J. You (2005)
Cancer Res. 65, 6811-6819
   Abstract »    Full Text »    PDF »
H-RAS V12-induced radioresistance in HCT116 colon carcinoma cells is heregulin dependent.
R. W. Caron, A. Yacoub, X. Zhu, C. Mitchell, S. I. Han, T. Sasazuki, S. Shirasawa, M. P. Hagan, S. Grant, and P. Dent (2005)
Mol. Cancer Ther. 4, 243-255
   Abstract »    Full Text »    PDF »
Activated forms of H-RAS and K-RAS differentially regulate membrane association of PI3K, PDK-1, and AKT and the effect of therapeutic kinase inhibitors on cell survival.
R. W. Caron, A. Yacoub, M. Li, X. Zhu, C. Mitchell, Y. Hong, W. Hawkins, T. Sasazuki, S. Shirasawa, A. P. Kozikowski, et al. (2005)
Mol. Cancer Ther. 4, 257-270
   Abstract »    Full Text »    PDF »
A Phase I Trial of the Dual Farnesyltransferase and Geranylgeranyltransferase Inhibitor L-778,123 and Radiotherapy for Locally Advanced Pancreatic Cancer.
N. E. Martin, T. B. Brunner, K. D. Kiel, T. F. DeLaney, W. F. Regine, M. Mohiuddin, E. F. Rosato, D. G. Haller, J. P. Stevenson, D. Smith, et al. (2004)
Clin. Cancer Res. 10, 5447-5454
   Abstract »    Full Text »    PDF »
Oncogenic H-Ras Up-Regulates Expression of ERCC1 to Protect Cells from Platinum-Based Anticancer Agents.
C.-K. Youn, M.-H. Kim, H.-J. Cho, H.-B. Kim, I.-Y. Chang, M.-H. Chung, and H. J. You (2004)
Cancer Res. 64, 4849-4857
   Abstract »    Full Text »    PDF »
Epidermal Growth Factor Receptor Autocrine Signaling in RIE-1 Cells Transformed by the Ras Oncogene Enhances Radiation Resistance.
T. M. Grana, C. I. Sartor, and A. D. Cox (2003)
Cancer Res. 63, 7807-7814
   Abstract »    Full Text »    PDF »
Farnesyltransferase Inhibitors: An Overview of the Results of Preclinical and Clinical Investigations.
T. B. Brunner, S. M. Hahn, A. K. Gupta, R. J. Muschel, W. G. McKenna, and E. J. Bernhard (2003)
Cancer Res. 63, 5656-5668
   Abstract »    Full Text »    PDF »
DNA-PKcs Expression in Esophageal Cancer as a Predictor for Chemoradiation Therapeutic Sensitivity.
T. Noguchi, T. Shibata, S. Fumoto, Y. Uchida, W. Mueller, and S. Takeno (2002)
Ann. Surg. Oncol. 9, 1017-1022
   Abstract »    Full Text »    PDF »
Ras Mediates Radioresistance through Both Phosphatidylinositol 3-Kinase-dependent and Raf-dependent but Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase Kinase-independent Signaling Pathways.
T. M. Grana, E. V. Rusyn, H. Zhou, C. I. Sartor, and A. D. Cox (2002)
Cancer Res. 62, 4142-4150
   Abstract »    Full Text »    PDF »
Akt Enhances Mdm2-mediated Ubiquitination and Degradation of p53.
Y. Ogawara, S. Kishishita, T. Obata, Y. Isazawa, T. Suzuki, K. Tanaka, N. Masuyama, and Y. Gotoh (2002)
J. Biol. Chem. 277, 21843-21850
   Abstract »    Full Text »    PDF »
Oncogenic H-Ras Enhances DNA Repair through the Ras/Phosphatidylinositol 3-Kinase/Rac1 Pathway in NIH3T3 Cells. EVIDENCE FOR ASSOCIATION WITH REACTIVE OXYGEN SPECIES.
H.-J. Cho, H. G. Jeong, J.-S. Lee, E.-R. Woo, J.-W. Hyun, M.-H. Chung, and H. J. You (2002)
J. Biol. Chem. 277, 19358-19366
   Abstract »    Full Text »    PDF »
A Phase I Trial of the Farnesyltransferase Inhibitor L-778,123 and Radiotherapy for Locally Advanced Lung and Head and Neck Cancer.
S. M. Hahn, E. J. Bernhard, W. Regine, M. Mohiuddin, D. G. Haller, J. P. Stevenson, D. Smith, B. Pramanik, J. Tepper, T. F. DeLaney, et al. (2002)
Clin. Cancer Res. 8, 1065-1072
   Abstract »    Full Text »    PDF »
Inhibition of Radiation-induced Nuclear Factor-{kappa}B Activation by an Anti-Ras Single-Chain Antibody Fragment: Lack of Involvement in Radiosensitization.
J. S. Russell, U. Raju, G. J. Gumin, F. F. Lang, D. R. Wilson, T. Huet, and P. J. Tofilon (2002)
Cancer Res. 62, 2318-2326
   Abstract »    Full Text »    PDF »
Noninvasive Imaging of Tumor Redox Status and Its Modification by Tissue Glutathione Levels.
P. Kuppusamy, H. Li, G. Ilangovan, A. J. Cardounel, J. L. Zweier, K. Yamada, M. C. Krishna, and J. B. Mitchell (2002)
Cancer Res. 62, 307-312
   Abstract »    Full Text »    PDF »
Hepatoma-derived Growth Factor Is Associated with Reduced Sensitivity to Irradiation in Esophageal Cancer.
A. Matsuyama, H. Inoue, K. Shibuta, Y. Tanaka, G. F. Barnard, K. Sugimachi, and M. Mori (2001)
Cancer Res. 61, 5714-5717
   Abstract »    Full Text »    PDF »
Blocking Oncogenic Ras Signaling for Cancer Therapy.
A. A. Adjei (2001)
J Natl Cancer Inst 93, 1062-1074
   Abstract »    Full Text »    PDF »
Direct Evidence for the Contribution of Activated N-ras and K-ras Oncogenes to Increased Intrinsic Radiation Resistance in Human Tumor Cell Lines.
E. J. Bernhard, E. J. Stanbridge, S. Gupta, A. K. Gupta, D. Soto, V. J. Bakanauskas, G. J. Cerniglia, R. J. Muschel, and W. G. McKenna (2000)
Cancer Res. 60, 6597-6600
   Abstract »    Full Text »
Control of the eukaryotic cell cycle by MAP kinase signaling pathways.
M. G. WILKINSON and J. B. A. MILLAR (2000)
FASEB J 14, 2147-2157
   Abstract »    Full Text »
Restricted 12p Amplification and RAS Mutation in Human Germ Cell Tumors of the Adult Testis.
H. Roelofs, M. C. Mostert, K. Pompe, G. Zafarana, M. van Oorschot, R. J. H. L. M. van Gurp, A. J. M. Gillis, H. Stoop, B. Beverloo, J. W. Oosterhuis, et al. (2000)
Am. J. Pathol. 157, 1155-1166
   Abstract »    Full Text »    PDF »
Oncogenic Ras Sensitizes Cells to Apoptosis by Par-4.
A. Nalca, S. G. Qiu, N. El-Guendy, S. Krishnan, and V. M. Rangnekar (1999)
J. Biol. Chem. 274, 29976-29983
   Abstract »    Full Text »    PDF »
Radiosensitization of Human Tumor Cell Lines Induced by the Adenovirus-mediated Expression of an Anti-Ras Single-Chain Antibody Fragment.
J. S. Russell, F. F. Lang, T. Huet, M. Janicot, S. Chada, D. R. Wilson, and P. J. Tofilon (1999)
Cancer Res. 59, 5239-5244
   Abstract »    Full Text »    PDF »
Mitogen-activated Protein Kinase Kinase 2 Activation Is Essential for Progression through the G2/M Checkpoint Arrest in Cells Exposed to Ionizing Radiation.
D. W. Abbott and J. T. Holt (1999)
J. Biol. Chem. 274, 2732-2742
   Abstract »    Full Text »    PDF »
Apoptosis and Predisposition To Oral Cancer.
P. Polverini and J.E. Nor (1999)
Critical Reviews in Oral Biology & Medicine 10, 139-152
   Abstract »    Full Text »    PDF »
Conversion of a radioresistant phenotype to a more sensitive one by disabling erbB receptor signaling in human cancer cells.
D. M. O'Rourke, G. D. Kao, N. Singh, B.-W. Park, R. J. Muschel, C.-j. Wu, and M. I. Greene (1998)
PNAS 95, 10842-10847
   Abstract »    Full Text »    PDF »
K-ras mutations in patients with early colorectal cancers.
H J N Andreyev, J V T Tilsed, D Cunningham, S A Sampson, A R Norman, H J Schneider, and P A Clarke (1997)
Gut 41, 323-329
   Abstract »    Full Text »    PDF »
c-Jun NH2-terminal Kinase Regulation of the Apoptotic Response of Small Cell Lung Cancer Cells to Ultraviolet Radiation.
L. Butterfield, B. Storey, L. Maas, and L. E. Heasley (1997)
J. Biol. Chem. 272, 10110-10116
   Abstract »    Full Text »    PDF »
Radiation Oncology.
J. D. Cox (1991)
JAMA 265, 3165-3167
   Abstract »    PDF »
Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma.
U Kasid, A Pfeifer, T Brennan, M Beckett, R. Weichselbaum, A Dritschilo, and G. Mark (1989)
Science 243, 1354-1356
   Abstract »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)