Cancer Research The Future of Cancer Research: Science and Patient Impact
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 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 Gu, J.
Right arrow Articles by Fang, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gu, J.
Right arrow Articles by Fang, B.
[Cancer Research 60, 5359-5364, October 1, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Tumor-specific Transgene Expression from the Human Telomerase Reverse Transcriptase Promoter Enables Targeting of the Therapeutic Effects of the Bax Gene to Cancers1

Jian Gu, Shunsuke Kagawa, Masahiro Takakura, Satoru Kyo, Masaki Inoue, Jack A. Roth and Bingliang Fang2

Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [J. G., S. Ka., J. A. R., B. F.], and Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Ishikawa 920-0934, Japan [M. T., S. Ky., M. I.]

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly active in immortalized cells and >85% of human cancers but is quiescent in most normal somatic cells. To test the feasibility of using the hTERT promoter to induce tumor-specific transgene expression in cancer gene therapy, we constructed an adenoviral vector expressing a LacZ reporter gene driven by the hTERT core promoter and evaluated its activity in vitro and in vivo. The hTERT promoter could drive high-level expression of LacZ in tumor cells but not in normal cells and normal mouse tissues. Using a binary adenoviral system that can induce Bax gene expression, we showed that induction of the Bax gene expression via the hTERT promoter elicited tumor-specific apoptosis in vitro, suppressed tumor growth in nude mice, and prevented the toxicity of the Bax gene in vitro and in vivo. Thus, the hTERT promoter is apparently a strong and tumor-selective promoter with potential application in targeted cancer gene therapy.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
W. Guo, S. Wu, J. Liu, and B. Fang
Identification of a Small Molecule with Synthetic Lethality for K-Ras and Protein Kinase C Iota
Cancer Res., September 15, 2008; 68(18): 7403 - 7408.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Zhang, R. Komaki, L. Wang, B. Fang, and J. Y. Chang
Treatment of Radioresistant Stem-Like Esophageal Cancer Cells by an Apoptotic Gene-Armed, Telomerase-Specific Oncolytic Adenovirus
Clin. Cancer Res., May 1, 2008; 14(9): 2813 - 2823.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J. Li, S. Lad, G. Yang, Y. Luo, M. Iacobelli-Martinez, F. J. Primus, R. A. Reisfeld, and E. Li
Adenovirus Fiber Shaft Contains a Trimerization Element That Supports Peptide Fusion for Targeted Gene Delivery
J. Virol., December 15, 2006; 80(24): 12324 - 12331.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G.-S. Shieh, A.-L. Shiau, Y.-T. Yo, P.-R. Lin, C.-C. Chang, T.-S. Tzai, and C.-L. Wu
Low-Dose Etoposide Enhances Telomerase-Dependent Adenovirus-Mediated Cytosine Deaminase Gene Therapy through Augmentation of Adenoviral Infection and Transgene Expression in a Syngeneic Bladder Tumor Model.
Cancer Res., October 15, 2006; 66(20): 9957 - 9966.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
T. Miyoshi, S. Hirohata, H. Ogawa, M. Doi, M. Obika, T. Yonezawa, Y. Sado, S. Kusachi, S. Kyo, S. Kondo, et al.
Tumor-specific expression of the RGD-{alpha}3(IV)NC1 domain suppresses endothelial tube formation and tumor growth in mice
FASEB J, September 1, 2006; 20(11): 1904 - 1906.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Dong, L. Wang, J. J. Davis, W. Hu, L. Zhang, W. Guo, F. Teraishi, L. Ji, and B. Fang
Eliminating Established Tumor in nu/nu Nude Mice by a Tumor Necrosis Factor-{alpha}-Related Apoptosis-Inducing Ligand-Armed Oncolytic Adenovirus
Clin. Cancer Res., September 1, 2006; 12(17): 5224 - 5230.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
H. Ito, H. Aoki, F. Kuhnel, Y. Kondo, S. Kubicka, T. Wirth, E. Iwado, A. Iwamaru, K. Fujiwara, K. R. Hess, et al.
Autophagic cell death of malignant glioma cells induced by a conditionally replicating adenovirus.
J Natl Cancer Inst, May 3, 2006; 98(9): 625 - 636.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Teraishi, S. Wu, L. Zhang, W. Guo, J. J. Davis, F. Dong, and B. Fang
Identification of a Novel Synthetic Thiazolidin Compound Capable of Inducing c-Jun NH2-Terminal Kinase-Dependent Apoptosis in Human Colon Cancer Cells
Cancer Res., July 15, 2005; 65(14): 6380 - 6387.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
F. Teraishi, S. Wu, J. Sasaki, L. Zhang, H.-B. Zhu, J. J. Davis, and B. Fang
P-Glycoprotein-Independent Apoptosis Induction by a Novel Synthetic Compound, MMPT [5-[(4-Methylphenyl)methylene]-2-(phenylamino)-4(5H)-thiazolone]
J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 355 - 362.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Z.-Z. Su, D. Sarkar, L. Emdad, G. J. Duigou, C. S. H. Young, J. Ware, A. Randolph, K. Valerie, and P. B. Fisher
Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter
PNAS, January 25, 2005; 102(4): 1059 - 1064.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
R. M. Reddy, W. S. Tsai, M. F. Ziauddin, J. Zuo, G. W. Cole Jr, J. B. Maxhimer, B. Fang, D. S. Schrump, and D. M. Nguyen
Cisplatin enhances apoptosis induced by a tumor-selective adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand
J. Thorac. Cardiovasc. Surg., December 1, 2004; 128(6): 883 - 891.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
A. Biroccio and C. Leonetti
Telomerase as a new target for the treatment of hormone-refractory prostate cancer
Endocr. Relat. Cancer, September 1, 2004; 11(3): 407 - 421.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Q. Zhang, M. Nie, J. Sham, C. Su, H. Xue, D. Chua, W. Wang, Z. Cui, Y. Liu, C. Liu, et al.
Effective Gene-Viral Therapy for Telomerase-Positive Cancers by Selective Replicative-Competent Adenovirus Combining with Endostatin Gene
Cancer Res., August 1, 2004; 64(15): 5390 - 5397.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Jacob, J. Davis, H. Zhu, L. Zhang, F. Teraishi, S. Wu, F. C. Marini III, and B. Fang
Suppressing Orthotopic Pancreatic Tumor Growth with a Fiber-Modified Adenovector Expressing the TRAIL Gene from the Human Telomerase Reverse Transcriptase Promoter
Clin. Cancer Res., May 15, 2004; 10(10): 3535 - 3541.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. C. Hahn
Targeting Cancer with Telomerase: Commentary re Q. Huang et al., A Novel Conditionally Replicative Adenovirus Vector Targeting Telomerase-Positive Tumor Cells. Clin. Cancer Res., 10: 1439-1445, 2004.
Clin. Cancer Res., February 15, 2004; 10(4): 1203 - 1205.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
S. Wu, H. Zhu, J. Gu, L. Zhang, F. Teraishi, J. J. Davis, D. A. Jacob, and B. Fang
Induction of Apoptosis and Down-Regulation of Bcl-XL in Cancer Cells by a Novel Small Molecule, 2[ [3-(2,3-Dichlorophenoxy)propyl]amino]ethanol
Cancer Res., February 1, 2004; 64(3): 1110 - 1113.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Fukazawa, Y. Maeda, F. M. Sladek, and L. B. Owen-Schaub
Development of a Cancer-Targeted Tissue-Specific Promoter System
Cancer Res., January 1, 2004; 64(1): 363 - 369.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Kawashima, S. Kagawa, N. Kobayashi, Y. Shirakiya, T. Umeoka, F. Teraishi, M. Taki, S. Kyo, N. Tanaka, and T. Fujiwara
Telomerase-Specific Replication-Selective Virotherapy for Human Cancer
Clin. Cancer Res., January 1, 2004; 10(1): 285 - 292.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. A. Lanson Jr., P. L. Friedlander, P. Schwarzenberger, J. K. Kolls, and G. Wang
Replication of an Adenoviral Vector Controlled by the Human Telomerase Reverse Transcriptase Promoter Causes Tumor-Selective Tumor Lysis
Cancer Res., November 15, 2003; 63(22): 7936 - 7941.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Moon, Y. Oh, and J. A. Roth
Current Status of Gene Therapy for Lung Cancer and Head and Neck Cancer
Clin. Cancer Res., November 1, 2003; 9(14): 5055 - 5067.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
M. H. Katz, D. E. Spivack, S. Takimoto, B. Fang, D. W. Burton, A.R. Moossa, R. M. Hoffman, and M. Bouvet
Gene Therapy of Pancreatic Cancer With Green Fluorescent Protein and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Fusion Gene Expression Driven by a Human Telomerase Reverse Transcriptase Promoter
Ann. Surg. Oncol., August 1, 2003; 10(7): 762 - 772.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Takeda, H. Inaba, M. Yamazaki, S. Kyo, T. Miyamoto, S. Suzuki, T. Ehara, T. Kakizawa, M. Hara, L. J. DeGroot, et al.
Tumor-Specific Gene Therapy for Undifferentiated Thyroid Carcinoma Utilizing the Telomerase Reverse Transcriptase Promoter
J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3531 - 3538.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Wirth, L. Zender, B. Schulte, B. Mundt, R. Plentz, K. L. Rudolph, M. Manns, S. Kubicka, and F. Kuhnel
A Telomerase-dependent Conditionally Replicating Adenovirus for Selective Treatment of Cancer
Cancer Res., June 15, 2003; 63(12): 3181 - 3188.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
W. C. Hahn
Role of Telomeres and Telomerase in the Pathogenesis of Human Cancer
J. Clin. Oncol., May 15, 2003; 21(10): 2034 - 2043.
[Abstract] [Full Text] [PDF]

Home page
 Vet PatholHome page
D. J. Argyle and L. Nasir
Telomerase: A Potential Diagnostic and Therapeutic Tool in Canine Oncology
Vet. Pathol., January 1, 2003; 40(1): 1 - 7.
[Abstract] [Full Text] [PDF]

Home page
 Microbiol. Mol. Biol. Rev.Home page
Y.-S. Cong, W. E. Wright, and J. W. Shay
Human Telomerase and Its Regulation
Microbiol. Mol. Biol. Rev., September 1, 2002; 66(3): 407 - 425.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
I. Horikawa, P. L. Cable, S. J. Mazur, E. Appella, C. A. Afshari, and J. C. Barrett
Downstream E-Box-mediated Regulation of the Human Telomerase Reverse Transcriptase (hTERT) Gene Transcription: Evidence for an Endogenous Mechanism of Transcriptional Repression
Mol. Biol. Cell, August 1, 2002; 13(8): 2585 - 2597.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Lin, J. Gu, L. Zhang, X. Huang, L. C. Stephens, S. A. Curley, and B. Fang
Targeted Expression of Green Fluorescent Protein/Tumor Necrosis Factor-related Apoptosis-inducing Ligand Fusion Protein from Human Telomerase Reverse Transcriptase Promoter Elicits Antitumor Activity without Toxic Effects on Primary Human Hepatocytes
Cancer Res., July 1, 2002; 62(13): 3620 - 3625.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J.-L. Mergny, J.-F. Riou, P. Mailliet, M.-P. Teulade-Fichou, and E. Gilson
Natural and pharmacological regulation of telomerase
Nucleic Acids Res., February 15, 2002; 30(4): 839 - 865.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
F. Andriani, B. Nan, J. Yu, X. Li, N. L. Weigel, M. J. McPhaul, S. Kasper, S. Kagawa, B. Fang, R. J. Matusik, et al.
Use of the Probasin Promoter ARR2PB to Express Bax in Androgen Receptor-Positive Prostate Cancer Cells
J Natl Cancer Inst, September 5, 2001; 93(17): 1314 - 1324.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. Komata, Y. Kondo, T. Kanzawa, S. Hirohata, S. Koga, H. Sumiyoshi, S. M. Srinivasula, B. P. Barna, I. M. Germano, M. Takakura, et al.
Treatment of Malignant Glioma Cells with the Transfer of Constitutively Active Caspase-6 Using the Human Telomerase Catalytic Subunit (Human Telomerase Reverse Transcriptase) Gene Promoter
Cancer Res., August 1, 2001; 61(15): 5796 - 5802.
[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 © 2000 by the American Association for Cancer Research.