Abstract:
:HeLa cell cultures were used as model systems for small interfering RNA (siRNA) induced knockdown of mRNA expression of the human telomerase catalytic subunit, telomerase reverse transcriptase (hTERT). Four 21-bp siRNAs targeting different sites of the hTERT mRNA were designed, and the siRNA molecules produced by a T7 transcription system in vitro. In transient transfection assays on HeLa cells, only one of the tested siRNAs produced a potent knockdown effect on hTERT mRNA expression, associated with the suppression of telomerase activity (both reduced by approximately 50%). An expression vector encoding a hairpin siRNA against the effective hTERT mRNA target site was generated, and HeLa clones stably expressing hTERT-specific siRNA were created. Two clones showed extremely reduced hTERT mRNA expression, associated with unusually short telomeres, the inhibition of cell growth and the induction of senescence and apoptosis. Thus, there was obvious loss of viability in cells lacking hTERT expression and carrying short telomeres. This was most prominent in the clone that showed prolonged reductions (over two months) in both hTERT expression and telomerase activity. Thus, our data clearly show that long-term suppression of telomerase expression by siRNA is an attainable goal, at least in a HeLa cell model system.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Kurvinen K,Syrjänen S,Johansson Bsubject
Has Abstractpub_date
2006-07-01 00:00:00pages
279-88issue
1eissn
1019-6439issn
1791-2423journal_volume
29pub_type
杂志文章abstract::Malignant astrocytomas are highly invasive, vascular neoplasms that comprise the majority of nervous system tumors in humans. A strong association has previously been made between malignancy in human astrocytic tumors and increased expression of certain fibroblast growth factor (FGF) family members. MG-160 is an intri...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 已发布勘误
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doi:
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doi:
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journal_title:International journal of oncology
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