We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
In vitro study of HIF-1 activation and VEGF release by bFGF in the T47D breast cancer cell line under normoxic conditions: involvement of PI-3K/Akt and MEK1/ERK pathways.
Journal of Pathology 2005 March
Hypoxia-inducible factor (HIF) is critical in the modulation of tumour angiogenesis in response to hypoxia. In the present study, the mechanisms underlying basic fibroblast growth factor (bFGF)-induced activation of HIF-1 and the subsequent release of vascular endothelial growth factor (VEGF) in a human breast cancer cell line (T47D) under normoxic conditions were explored. The data show that HIF-1alpha expression is induced by bFGF in a dose- and time-dependent fashion, while increased HIF-1alpha protein expression and transactivity of HIF-1 are due to the phosphorylation of Akt by bFGF, as indicated by application of the phosphatidylinositol 3-kinase (PI-3K) inhibitor LY294002. The data also show that the MEK1 (mitogen-activated protein kinase kinase-1)/ERK (extracellular signal-regulated kinase) pathway is only involved in bFGF-induced transactivity of HIF-1, but not HIF-1alpha expression, indicating roles for both the PI-3K/Akt and the MEK1/ERK pathways in bFGF activity. In addition, the translation inhibitor cycloheximide confirmed that bFGF-induced HIF-1alpha protein expression was due to de novo protein synthesis. In contrast, p38 was not required for the expression of HIF-1alpha or HIF-1 transactivity, although significant phosphorylation of p38 was observed after bFGF treatment. Treatment of the cells with bFGF increased the amount of VEGF release, and this could be suppressed by either PD98059 or LY294002, suggesting the presence of a HIF-1alpha-dependent pathway for bFGF-induced VEGF production. In conclusion, the PI-3K/Akt and MEK1/ERK pathways, in a potentially independent and co-operative fashion, can modulate HIF-1 activation by bFGF. Further studies will pinpoint whether HIF-1 is the transcriptional factor responsible for the increased VEGF production following bFGF treatment of breast tumour cells.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app