uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Hypoxia mediated up-regulation of telomerase activity in neuroblastoma cell lines
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
Show others and affiliations
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-94109OAI: oai:DiVA.org:uu-94109DiVA: diva2:167852
Available from: 2006-03-17 Created: 2006-03-17 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Activity and Regulation of Telomerase in Malignant Cells
Open this publication in new window or tab >>Activity and Regulation of Telomerase in Malignant Cells
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

An important step in tumorgenesis is the acquisition of cellular immortality. Tumor cells accomplish this by activating the enzyme telomerase, and thereby avoiding replicative senescence. The aim of this thesis was to study the activity and regulation of telomerase in a panel of malignant cell types.

We found that TGF-β1 (transforming growth factor-β1) mediated differential effects on telomerase activity in five ATC (anaplastic thyroid carcinoma) cell lines. Cells that harbored a p53 mutation responded by up-regulation of telomerase activity after TGF-β1 treatment, whereas cell lines displaying wt p53 responded by down-regulation of telomerase activity. Thus, these results indicate a possible connection between p53 genotype and telomerase response to TGF-β1 treatment. Furthermore, the decreased telomerase activity appeared to be due to transcriptional repression of the hTERT promoter and the increased activity possibly involved hTERT activation via phosphorylation.

We have previously shown that IFNs (interferons) sensitize MM (multiple myeloma) cells to Fas-mediated apoptosis. In the present investigation both IFN-α and IFN-γ down regulated telomerase activity in the MM cell line U-266-1970. The mechanism underlying the reduction of telomerase activity by IFN was shown to be transcriptional repression of the hTERT gene. We suggest that one potential mechanism whereby IFN sensitize MM cells to Fas-mediated apoptosis is by repressing hTERT activity at the transcriptional level.

In the next study we demonstrated that basal telomerase activity is not a key determinant of sensitivity to cytotoxic drugs in ESCC (esophageal squamous cell carcinoma) cell lines. Furthermore, we observed no correlation between c-Myc amplification, p53 mutations and high telomerase activity levels in these cell lines.

Finally, neuroblastoma cell lines were shown to up-regulate telomerase activity in response to hypoxic exposure and the main regulatory mechanism was not mediated by increased hTERT mRNA expression. This finding might constitute an adaptive stress response of tumor cells exposed to hypoxia.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 119
Keyword
Medicine, apoptosis, ATC, c-Myc, drug sensitivity, ESCC, hTERT, hypoxia, IFN, MM, neuroblastoma, p53, telomerase, TGF-β, Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-6623 (URN)91-554-6486-6 (ISBN)
Public defence
2006-04-07, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjöldsväg 20, Uppsala, 13:15
Opponent
Supervisors
Available from: 2006-03-17 Created: 2006-03-17Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Genetics and Pathology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 425 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf