Cancer Research Cell Death Mechanisms and Cancer Therapy Sign up for Cancer Research eTOC's
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, S.
Right arrow Articles by El-Deiry, W. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S.
Right arrow Articles by El-Deiry, W. S.
[Cancer Research 64, 6666-6672, September 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Inducible Silencing of KILLER/DR5 In vivo Promotes Bioluminescent Colon Tumor Xenograft Growth and Confers Resistance to Chemotherapeutic Agent 5-Fluorouracil

Shulin Wang and Wafik S. El-Deiry

Departments of Medicine, Genetics, and Pharmacology, and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

The candidate tumor suppressor KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor for the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a promising agent for cancer therapy. The majority of studies on KILLER/DR5 have been focused on its role in TRAIL-induced apoptosis. However, its contribution to the inhibition of tumor growth and its role as a determinant of chemosensitivity are poorly understood. In the present study, we have generated stable human colon cancer cell lines, in which the function of KILLER/DR5 was ablated using inducible RNA interference. Inducible silencing of KILLER/DR5 in vivo by exposure of mice to doxycycline led to accelerated growth of bioluminescent tumor xenografts and conferred resistance to the chemotherapeutic agent 5-fluorouracil. Our results suggest that KILLER/DR5 may be a critical determinant for tumorigenicity and chemosensitivity.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
A. Elias, M. D. Siegelin, A. Steinmuller, A. von Deimling, U. Lass, B. Korn, and W. Mueller
Epigenetic Silencing of Death Receptor 4 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Gliomas
Clin. Cancer Res., September 1, 2009; 15(17): 5457 - 5465.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. S. Hart and W. S. El-Deiry
Invincible, but Not Invisible: Imaging Approaches Toward In Vivo Detection of Cancer Stem Cells
J. Clin. Oncol., June 10, 2008; 26(17): 2901 - 2910.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
L. Cao, P. Du, S.-H. Jiang, G.-H. Jin, Q.-L. Huang, and Z.-C. Hua
Enhancement of antitumor properties of TRAIL by targeted delivery to the tumor neovasculature
Mol. Cancer Ther., April 1, 2008; 7(4): 851 - 861.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. M. Laguinge, R. N. Samara, W. Wang, W. S. El-Deiry, G. Corner, L. Augenlicht, L. Mishra, and J. M. Jessup
DR5 Receptor Mediates Anoikis in Human Colorectal Carcinoma Cell Lines
Cancer Res., February 1, 2008; 68(3): 909 - 917.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Bin, J. Thorburn, L. R. Thomas, P. E. Clark, R. Humphreys, and A. Thorburn
Tumor-derived Mutations in the TRAIL Receptor DR5 Inhibit TRAIL Signaling through the DR4 Receptor by Competing for Ligand Binding
J. Biol. Chem., September 21, 2007; 282(38): 28189 - 28194.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. R. Wilson, K. M. McLaughlin, M. McEwan, H. Sakai, K. M.A. Rogers, K. M. Redmond, P. G. Johnston, and D. B. Longley
c-FLIP: A Key Regulator of Colorectal Cancer Cell Death
Cancer Res., June 15, 2007; 67(12): 5754 - 5762.
[Abstract] [Full Text] [PDF]

Home page
 Mol Cancer ResHome page
T. Yoshida, T. Maoka, S. K. Das, K. Kanazawa, M. Horinaka, M. Wakada, Y. Satomi, H. Nishino, and T. Sakai
Halocynthiaxanthin and Peridinin Sensitize Colon Cancer Cell Lines to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand
Mol. Cancer Res., June 1, 2007; 5(6): 615 - 625.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. N. Samara, L. M. Laguinge, and J. M. Jessup
Carcinoembryonic Antigen Inhibits Anoikis in Colorectal Carcinoma Cells by Interfering with Trail-R2 (DR5) Signaling
Cancer Res., May 15, 2007; 67(10): 4774 - 4782.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Behbakht, L. Qamar, C. S. Aldridge, R. D. Coletta, S. A. Davidson, A. Thorburn, and H. L. Ford
Six1 Overexpression in Ovarian Carcinoma Causes Resistance to TRAIL-Mediated Apoptosis and Is Associated with Poor Survival
Cancer Res., April 1, 2007; 67(7): 3036 - 3042.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. M. van Geelen, J. L. Westra, E. G. de Vries, W. Boersma-van Ek, N. Zwart, H. Hollema, H. M. Boezen, N. H. Mulder, J. T. Plukker, S. de Jong, et al.
Prognostic Significance of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand and Its Receptors in Adjuvantly Treated Stage III Colon Cancer Patients
J. Clin. Oncol., November 1, 2006; 24(31): 4998 - 5004.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Kappel, Y. Matthess, B. Zimmer, M. Kaufmann, and K. Strebhardt
Tumor inhibition by genomically integrated inducible RNAi-cassettes
Nucleic Acids Res., September 11, 2006; 34(16): 4527 - 4536.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
T.-a. Matsui, Y. Sowa, T. Yoshida, H. Murata, M. Horinaka, M. Wakada, R. Nakanishi, T. Sakabe, T. Kubo, and T. Sakai
Sulforaphane enhances TRAIL-induced apoptosis through the induction of DR5 expression in human osteosarcoma cells
Carcinogenesis, September 1, 2006; 27(9): 1768 - 1777.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W. Wang, S.-H. Kim, and W. S. El-Deiry
Small-molecule modulators of p53 family signaling and antitumor effects in p53-deficient human colon tumor xenografts
PNAS, July 18, 2006; 103(29): 11003 - 11008.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Wang and W. S. El-Deiry
p73 or p53 Directly Regulates Human p53 Transcription to Maintain Cell Cycle Checkpoints.
Cancer Res., July 15, 2006; 66(14): 6982 - 6989.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
W. S. El-Deiry, C. C. Sigman, and G. J. Kelloff
Imaging and Oncologic Drug Development
J. Clin. Oncol., July 10, 2006; 24(20): 3261 - 3273.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. G.E. de Vries, J. A. Gietema, and S. de Jong
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Pathway and Its Therapeutic Implications
Clin. Cancer Res., April 15, 2006; 12(8): 2390 - 2393.
[Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
M. Horinaka, T. Yoshida, T. Shiraishi, S. Nakata, M. Wakada, and T. Sakai
The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand.
Mol. Cancer Ther., April 1, 2006; 5(4): 945 - 951.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
W. S. El-Deiry
The Promise of Optical Technologies for Measuring Tumor Response in Cancer Therapy Trials
Am. Assoc. Cancer Res. Educ. Book, April 1, 2006; 2006(1): 143 - 146.
[Full Text] [PDF]

Home page
 BloodHome page
H. Hasegawa, Y. Yamada, K. Komiyama, M. Hayashi, M. Ishibashi, T. Yoshida, T. Sakai, T. Koyano, T.-S. Kam, K. Murata, et al.
Dihydroflavonol BB-1, an extract of natural plant Blumea balsamifera, abrogates TRAIL resistance in leukemia cells
Blood, January 15, 2006; 107(2): 679 - 688.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Shiraishi, T. Yoshida, S. Nakata, M. Horinaka, M. Wakada, Y. Mizutani, T. Miki, and T. Sakai
Tunicamycin Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Human Prostate Cancer Cells
Cancer Res., July 15, 2005; 65(14): 6364 - 6370.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Shetty, B. A. Graham, J. G. Brown, X. Hu, N. Vegh-Yarema, G. Harding, J. T. Paul, and S. B. Gibson
Transcription Factor NF-{kappa}B Differentially Regulates Death Receptor 5 Expression Involving Histone Deacetylase 1
Mol. Cell. Biol., July 1, 2005; 25(13): 5404 - 5416.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. S. El-Deiry
Meeting Report: The International Conference on Tumor Progression and Therapeutic Resistance
Cancer Res., June 1, 2005; 65(11): 4475 - 4484.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
N. Finnberg, J. J. Gruber, P. Fei, D. Rudolph, A. Bric, S.-H. Kim, T. F. Burns, H. Ajuha, R. Page, G. S. Wu, et al.
DR5 Knockout Mice Are Compromised in Radiation-Induced Apoptosis
Mol. Cell. Biol., March 1, 2005; 25(5): 2000 - 2013.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.