| Intensive inhibition of hTERT expression by a ribozyme induces rapid apoptosis of cancer cells through a telomere length-independent pathway. | |
| | |
MedLine Citation:
|
PMID: 16205109 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Restoration of telomerase activity is essential for most of the malignancies. Telomerase reverse transcriptase (TERT) is the key component of telomerase. In this study, we designed a hammerhead ribozyme against human telomerase reverse transcriptase (hTERT) and observed its growth inhibition and pro-apoptosis effects on cancer cells. The efficiency of this ribozyme was verified in in vitro cleavage experiment. A recombinant retrovirus was constructed to transduce the ribozyme to telomerase positive colon carcinoma cell line SW480 and gastric carcinoma cell line SGC7901. We found that the ribozyme could strongly inhibit hTERT expression and telomerase activity, resulting in rapid apoptosis of cancer cells. Shortening of telomere and replicative senescence were not observed before cell death, indicating intensive inhibition of hTERT expression can induce apoptosis by some mechanism(s) except telomere shortening and replicative senescence. This study suggests that hTERT exerts a direct antiapoptotic function in cancer cells. Anti-hTERT ribozyme might be a potential means in the therapy of telomerase-positive malignancies. |
| | |
Authors:
|
Zhi-Ming Hao; Jin-Yan Luo; Jin Cheng; Lei Li; Daling He; Quan-Ying Wang; Guang-Xiao Yang |
Related Documents
:
|
17936649 - Cancer: a matter of life cycle? 15479119 - Spontaneous cell transformation: karyoplasts derived from multinucleated cells produce ... 9449619 - Lobe-specific telomerase activity in the intact adult brown norway rat prostate and its... 15149599 - Telomere shortening triggers senescence of human cells through a pathway involving atm,... 20816839 - Hiv-tat-mediated delivery of an lpts functional fragment inhibits telomerase activity a... 10906069 - Telomere length in male germ cells is inversely correlated with telomerase activity. 6617889 - Fate of newly synthesized histones in g1 and g0 cells. 2455919 - Expression of thermotolerance following microinjection of glutathione disulfide. 10664069 - Expression of gm3 microdomains on the surfaces of murine fibroblasts correlates with in... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2005-10-13 |
Journal Detail:
|
Title: Cancer biology & therapy Volume: 4 ISSN: 1538-4047 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2005 Oct |
Date Detail:
|
Created Date: 2005-11-24 Completed Date: 2006-06-22 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 1098-103 Citation Subset: IM |
Affiliation:
|
Department of Gastroenterology, 1st Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. haozhm@public.xa.sn.cn |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Apoptosis / drug effects* Carcinoma / pathology Cell Line, Tumor Colonic Neoplasms / enzymology, genetics, pathology DNA, Recombinant / genetics DNA-Binding Proteins / antagonists & inhibitors*, genetics, metabolism* Humans Mice NIH 3T3 Cells RNA, Catalytic / metabolism, pharmacology* Retroviridae / genetics Stomach Neoplasms / enzymology, genetics, pathology Telomerase / antagonists & inhibitors*, genetics, metabolism* Telomere / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/DNA, Recombinant; 0/DNA-Binding Proteins; 0/RNA, Catalytic; 0/hammerhead ribozyme; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase; EC 2.7.7.49/Tert protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Implantation of a closed-loop stimulation in the management of medically refractory focal epilepsy: ...
Next Document: Polymorphism in the hypoxia-inducible factor 1alpha gene may confer susceptibility to androgen-indep...