A quantitative analysis of the reduction in oxygen levels required to induce up-regulation of vascular endothelial growth factor (VEGF) mRNA in cervical cancer cell lines
Open accessAbstract
The presence of hypoxia (low oxygen concentrations) in solid tumours correlates with poor prognosis, increased metastasis, and resistance to radiotherapy and some forms of chemotherapy. Malignant cells produce an angiogenesis factor, vascular endothelial growth factor (VEGF), which may increase metastatic ability and is up-regulated in the presence of hypoxia. Clinical data for cancers of the cervix and head and neck relate oxygen levels in the tumour to treatment outcome. This suggests the possibility that the presence of VEGF mRNA might be used as a marker for relevant levels of hypoxia. Suspension cultures of three human cervical cancer cell lines, SiHa, ME-180 and HeLa, were used to investigate up-regulation of VEGF mRNA levels following exposure to precisely defined oxygen concentrations for 2 or 4 h. An oxygen sensor was used to confirm the actual levels of dissolved oxygen present. The oxygen concentrations which caused half-maximal upregulation (the Km value) of VEGF mRNA level in the three cell lines were similar except for one instance (Km at 4 h: SiHa 27.0 +/- 5.7 microM, ME-180 16.8 +/- 3.3 microM, HeLa 13.0 +/- 1.8 microM, SiHa and HeLa P = 0.01). The Km values for the HeLa cell line as measured at 2 h (24.9 +/- 0.8 microM) and 4 h (13.0 +/- 1.8 microM) were significantly different (P < 0.0001). VEGF mRNA half-lives measured in air were consistent with values in the literature (SiHa 59.8 +/- 5.8 min, ME-180 44.4 +/- 7.2 min, HeLa 44.5 +/- 6.3 min). Differences in oxygen consumption at low oxygen concentrations were noted between the different cell lines. Stirring in suspension culture was found to induce VEGF mRNA in SiHa cells. The presence of VEGF mRNA may be a marker for radiobiologic hypoxia.
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Hypoxia-induced upregulation of HIF-1 leads to activation of VEGF.
“Hypoxia‐induced upregulation of HIF‐1 also leads to the activation of vascular endothelial growth factor (VEGF).”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [31]
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- Authors
- Chiarotto, J. A., & Hill, R. P.
- Affiliations
- University of Toronto (CA)
- ORCID
- Hill, R P
- Venue
- British Journal of Cancer
- Published
- 1999-06-25
- Volume
- 80
- Issue
- 10
- Pages
- 1518-1524
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2363165
- OpenAlex
- W1985531513
- Cited by
- 46
- References
- 53
- Citations by year
- 2023: 1 · 2021: 1 · 2016: 1
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Keywords
- vascular endothelial growth factor, VEGF mRNA, tumor hypoxia, oxygen concentration, cervical cancer cell lines, SiHa, HeLa, hypoxia markers, angiogenesis, oxygen consumption, mRNA half-life, stirring effects
- MeSH terms
- Uterine Cervical Neoplasms, Female, Half-Life, Humans, Lymphokines, Oxygen, RNA, Messenger, Tumor Cells, Cultured, Cell Hypoxia, Up-Regulation, Endothelial Growth Factors, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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