Regulation of c-jun expression during hypoxic and low-glucose stress.
Open Access
- 1 August 1994
- journal article
- Published by Taylor & Francis in Molecular and Cellular Biology
- Vol. 14 (8) , 5032-5042
- https://doi.org/10.1128/mcb.14.8.5032
Abstract
Hypoxic stress in tumor cells has been implicated in malignant progression and in the development of therapeutic resistance. We have investigated the effects of acute hypoxic exposure on regulation of the proto-oncogene c-jun in SiHa cells, a human squamous carcinoma cell line. Hypoxic exposure produced increased levels of c-jun mRNA resulting from both message stabilization and transcriptional activation. A superinduction of c-jun message resulted during simultaneous oxygen and glucose deprivation, with several characteristics of an induction mediated by oxidative-stress pathways. This superinduction was blocked by preincubation of cells with the glutathione precursor N-acetyl cysteine or with phorbol 12-myristate 13-acetate, which indicates redox control of c-jun expression and probable involvement of protein kinase C. By gel retardation assay, no increase in AP-1 DNA binding activity was found to be concomitant with the transcriptional activation of c-jun. A lack of increased DNA binding was observed for the consensus AP-1 sequence and for the two AP-1 sequence variants found within the c-Jun promoter. Additionally, hypoxic and low-glucose stress produced no activation of stably transfected AP-1 reporter sequences. Taken together, these results indicate that the transcriptional activation of c-jun during hypoxic and low-glucose stress involves redox control and is unlikely to be mediated by AP-1 recognition elements within the c-jun promoter.Keywords
This publication has 55 references indexed in Scilit:
- Transcription factors junB and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma development.Genes & Development, 1992
- Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesisNature, 1992
- Enhanced epidermal growth factor receptor synthesis in human squamous carcinoma cells exposed to low levels of oxygenInternational Journal of Cancer, 1992
- Phosphorylation of c-jun mediated by MAP kinasesNature, 1991
- Ha-Ras augments c-Jun activity and stimulates phosphorylation of its activation domainNature, 1991
- Redox Regulation of Fos and Jun DNA-Binding Activity in VitroScience, 1990
- THE PROTEIN KINASE C FAMILY: HETEROGENEITY AND ITS IMPLICATIONSAnnual Review of Biochemistry, 1989
- Parallel Association of Fos and Jun Leucine Zippers Juxtaposes DNA Binding DomainsScience, 1989
- Retrotransposon-like VL30 elements are efficiently induced in anoxic rat fibroblastsJournal of Molecular Biology, 1989
- The jun proto-oncogene is positively autoregulated by its product, Jun/AP-1Published by Elsevier ,1988