Sökning: WFRF:(Makino Yuichi)
> (2002) >
Hypoxia alters gene...
Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype.
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- Jögi, Annika (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Øra, Ingrid (författare)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Nilsson, Helén (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Lindeheim, Åsa (författare)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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Makino, Yuichi (författare)
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- Poellinger, Lorenz (författare)
- Karolinska Institutet
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- Axelson, Håkan (författare)
- Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine
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- Påhlman, Sven (författare)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2002-05-14
- 2002
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 99:10, s. 7021-7026
- Relaterad länk:
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http://www.ncbi.nlm.... (free)
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http://dx.doi.org/10... (free)
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Abstract
Ämnesord
Stäng
- Insufficient oxygen and nutrient supply often restrain solid tumor growth, and the hypoxia-inducible factors (HIF) 1 alpha and HIF-2 alpha are key transcription regulators of phenotypic adaptation to low oxygen levels. Moreover, mouse gene disruption studies have implicated HIF-2 alpha in embryonic regulation of tyrosine hydroxylase, a hallmark gene of the sympathetic nervous system. Neuroblastoma tumors originate from immature sympathetic cells, and therefore we investigated the effect of hypoxia on the differentiation status of human neuroblastoma cells. Hypoxia stabilized HIF-1 alpha and HIF-2 alpha proteins and activated the expression of known hypoxia-induced genes, such as vascular endothelial growth factor and tyrosine hydroxylase. These changes in gene expression also occurred in hypoxic regions of experimental neuroblastoma xenografts grown in mice. In contrast, hypoxia decreased the expression of several neuronal/neuroendocrine marker genes but induced genes expressed in neural crest sympathetic progenitors, for instance c-kit and Notch-1. Thus, hypoxia apparently causes dedifferentiation both in vitro and in vivo. These findings suggest a novel mechanism for selection of highly malignant tumor cells with stem-cell characteristics.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Pediatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Pediatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Non-U.S. Gov't
- Support
- Phenotype
- Chromaffin : cytology
- Paraganglia
- Oxygen : metabolism
- Neuropeptide Y : genetics
- Neuroblastoma
- Neural Crest : cytology
- Experimental
- Neoplasms
- Nude
- Mice
- Lymphokines : genetics
- Insulin-Like Growth Factor II : genetics
- Human
- Helix-Loop-Helix Motifs
- Hela Cells
- Trans-Activators : genetics
- Trans-Activators : metabolism
- Transcription Factors : genetics
- Transcription Factors : metabolism
- Heterologous
- Transplantation
- Tumor Cells
- Cultured
- Tyrosine 3-Monooxygenase : genetics
- Sympathetic Nervous System : metabolism
- Gene Expression
- Female
- Endothelial Growth Factors : genetics
- Down-Regulation
- DNA-Binding Proteins : genetics
- Cell Hypoxia
- Biological Markers
- Animal
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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