Abstract | BACKGROUND: The presence of hypoxic regions within solid tumors is associated with a more malignant tumor phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumors alter gene expression, resulting in resistance to therapy. To investigate the mechanisms by which cancer cells adapt to hypoxia, we looked for novel hypoxia-induced genes. METHODS: The transcriptional response to hypoxia in human glioblastoma cells was quantified with the use of serial analysis of gene expression. The time course of gene expression in response to hypoxia in a panel of various human tumor cell lines was measured by real-time polymerase chain reaction. Hypoxic regions of human carcinomas were chemically marked with pimonidazole. Immunohistochemistry and in situ hybridization were used to examine gene expression in the tumor's hypoxic regions. RESULTS: CONCLUSIONS: We have identified the genes that are transcriptionally activated within hypoxic malignant cells, a crucial first step in understanding the complex interactions driving hypoxia response. Within our catalogue of hypoxia-responsive genes are novel candidates for hypoxia-driven angiogenesis.
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Authors | A Lal, H Peters, B St Croix, Z A Haroon, M W Dewhirst, R L Strausberg, J H Kaanders, A J van der Kogel, G J Riggins |
Journal | Journal of the National Cancer Institute
(J Natl Cancer Inst)
Vol. 93
Issue 17
Pg. 1337-43
(Sep 05 2001)
ISSN: 0027-8874 [Print] United States |
PMID | 11535709
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Glycoproteins
- Hormones
- Tenascin
- teleocalcin
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Topics |
- Blotting, Western
- Cell Hypoxia
(genetics)
- Gene Expression Regulation, Neoplastic
- Glioblastoma
(chemistry, genetics)
- Glycoproteins
(analysis, genetics)
- Hormones
(analysis, genetics)
- Humans
- Immunohistochemistry
- In Situ Hybridization
- Neovascularization, Pathologic
(genetics)
- Polymerase Chain Reaction
(methods)
- Tenascin
(analysis, genetics)
- Time Factors
- Transcription, Genetic
- Tumor Cells, Cultured
- Up-Regulation
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