Objective
Arsenic contamination from both natural and industrial sources is a significant public health problem. Arsenite, the trivalent form of arsenic, is a strong tumour promoter associated with multiple types of cancer. Paradoxically, arsenite is also effective in treating acute promyelocytic leukemia.
The exact mechanism of arsenite activity is still unclear; however, it strongly induces three major intracellular signalling pathways, the ERK, SAPK and p38 MARK cascades, that control gene expression via the transcriptional regulator AP-1.
Within the ERK and SAPK cascades, specificity is conferred by organisation into distinguishable signalling modules assembled into large molecular complexes. Our recent data indicate that, in human osteosarcoma cells, the p38 pathway also contains different signalling modules activated selectively by arsenite and the antibiotic anisomycin.
This project will
- characterise the molecular organisation of the p38 cascade activated by arsenite in cancer-derived cell lines and
- use the novel genetic technique of RNA interference to selectively inactivate arsenite-indeed intracellular signalling.
We will use biochemistry and molecular biology techniques to analyse the molecular assemblies that mediate this selectivity within the p38 cascade. To address the role of the p38 cascade in the cellular response to arsenite, components of this cascade will be down-regulated using RNA interference.
These siRNAs will target different isoforms óf p38 and its activating kinases MKKs 3, 3b and 6. We will assess the effect of their elimination on the induction of genes encoding components of AP-1, such as c-fos, c-jun, andjunB.
Taken together, these two approaches will further our understanding of the mechanism by which arsenite can exert both carcinogenic and therapeutic effects, thereby opening potential avenues for blocking or potentiating arsenite activity.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences public health
- natural sciences biological sciences cell biology cell signaling
- natural sciences biological sciences genetics RNA
- natural sciences chemical sciences inorganic chemistry metalloids
- medical and health sciences clinical medicine oncology leukemia
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-5
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.