Journal article
Metabolic oxidative stress activates signal transduction and gene expression during glucose deprivation in human tumor cells
Free radical biology & medicine, Vol.26(3), pp.419-430
1999
DOI: 10.1016/S0891-5849(98)00217-2
PMID: 9895234
Abstract
The mechanism of glucose deprivation-induced activation of Lyn kinase (Lyn), c-Jun
N-terminal kinase 1 (JNK1) and increased expression of basic fibroblast growth factor (bFGF) and c-Myc was investigated in MCF-7/ADR adriamycin-resistant human breast carcinoma cells. Glucose deprivation significantly increased steady state levels of oxidized glutathione content (GSSG) and intracellular prooxidants (presumably hydroperoxides) as well as caused the activation of Lyn, JNK1, and the accumulation of bFGF and c-Myc mRNA. The suppression of GSSG accumulation and prooxidant production by treatment with the thiol antioxidant,
N-acetylcysteine, also suppressed all the increases in kinase activation and gene expression observed during glucose deprivation. In addition, glucose deprivation was shown to induce oxidative stress in IMR90 SV40 transformed human fibroblasts, indicating that this phenomena is not limited to the MCF-7/ADR cell line. These and previous observations from our laboratory show that glucose deprivation-induced oxidative stress in MCF-7/ADR cells activates signal transduction involving Lyn, JNK1, and mitogen activated protein kinases (ERK1/ERK2) which results in increased bFGF and c-Myc mRNA accumulation. These results provide support for the hypothesis that alterations in intracellular oxidation/reduction reactions link changes in glycolytic metabolism to signal transduction and gene expression in these human tumor cells.
Details
- Title: Subtitle
- Metabolic oxidative stress activates signal transduction and gene expression during glucose deprivation in human tumor cells
- Creators
- RobertV Blackburn - Department of Radiation Oncology William Beaumont Hospital Royal Oak Michigan 48073 USADouglasR Spitz - Section of Cancer Biology, Radiation Oncology Center, Washington University School of Medicine, 4511 Forest Park Blvd., Suite 411, St. Louis, MO 63108,USAXin Liu - Beaumont Hospital, Royal OakSandraS Galoforo - Department of Radiation Oncology, William Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak, Michigan 48073 USAJuliaE Sim - Forest ParkLisaA Ridnour - Forest ParkJennC Chen - William Beaumont HospitalBruceH Davis - William Beaumont HospitalPeterM Corry - Department of Radiation Oncology, William Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak, Michigan 48073 USAYongJ Lee - Department of Radiation Oncology, William Beaumont Hospital, 3601 W. Thirteen Mile Road, Royal Oak, Michigan 48073 USA
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.26(3), pp.419-430
- DOI
- 10.1016/S0891-5849(98)00217-2
- PMID
- 9895234
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 1999
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312970302771
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