| Upregulation of survivin during immortalization of nontransformed human fibroblasts transduced with telomerase reverse transcriptase. | |
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MedLine Citation:
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PMID: 19483728 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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These investigations demonstrate that expression of the inhibitor of apoptosis family member, survivin, is dramatically increased during immortalization of nontransformed human fibroblasts that were transduced with telomerase reverse transcriptase (hTERT). Expression of survivin in immortalized fibroblasts peaked during G(2)/M phase of the cell cycle. However, the upregulation of survivin was dissociated from the rate of proliferation and proportion of G(2)/M cells. Depletion of survivin from immortal fibroblasts increased sensitivity to stress-induced apoptosis and resulted in an accumulation of cells with 4N DNA content. Conversely, overexpression of survivin in mortal fibroblasts conferred resistance to apoptosis. In contrast, very low levels of survivin in proliferating parental fibroblasts had no bearing on sensitivity to apoptosis. The upregulation of survivin did not appear to be a direct consequence of hTERT transduction. However, repression of hTERT resulted in the rapid downregulation of survivin in telomerase-immortalized fibroblasts and tumor cell lines, but not in cells immortalized via an Alternative Lengthening of Telomeres mechanism. These results have important therapeutic implications, as telomerase and survivin are both broadly expressed in human cancers. Selection during the immortalization process for cells expressing high levels of survivin may account for the abundance of survivin in diverse tumor types. |
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Authors:
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J Yuan; B M-P Yang; Z-H Zhong; I Shats; M Milyavsky; V Rotter; R B Lock; R R Reddel; K L MacKenzie |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-01 |
Journal Detail:
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Title: Oncogene Volume: 28 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2009 Jul |
Date Detail:
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Created Date: 2009-07-23 Completed Date: 2009-08-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 2678-89 Citation Subset: IM |
Affiliation:
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Children's Cancer Institute Australia for Medical Research, New South Wales, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Cell Line Cell Transformation, Neoplastic / genetics, metabolism*, pathology Fibroblasts / metabolism Humans Microtubule-Associated Proteins / biosynthesis* Telomerase / genetics, metabolism* Transduction, Genetic Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/BIRC5 protein, human; 0/Microtubule-Associated Proteins; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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