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Functional characterization of products homologous to fission yeast multi-drug resistance determinants

Objectif



Research objectives and content
Pohl (Padl human homologue) is a novel and highly conserved component of the human 26S proteosome that confers resistance to some chemotherapic drugs when overexpressed in mammalian cells, as the homologue of fission yeast Padl (V. Spataro et al. J. Biol. Chem.. 272, 30470-30475,1997). We aim to study the significance of Pohl in human tumour cell multi-drug resistance by exploting the NCI panel of 6( tumour cell lines. In order to investigate the mechanism of drug resistance in more detail, expression of Pohl at different levels, by a regulatable expression system, will be carried out in a selected tumour cell line. Furthermore, in order to define the normal physiological role of Pohl I, its expression and activity will be analysed after exposure of the cells to some stresses, such as drug exposure and hypoxia. Crml is a second determinant of multi-drug resistance, conserved from yeast to human: whose function i! involved in nuclear export...Defect in this process could be relevant for tumour progression, since human Crml interacts with the potential oncogenic nucleosporin, encoded by CAN gene. We propose to use yeas genetics in order to identify mutant drugs resistance-inducing alleles of hCRM I, and to perform immunochemical analysis of hCRM I expression.
Training content (objective, benefit and expected impact)
The aim is to achieve a better and comprehensive understanding of the extent and nature of involvement a these new genes in human tumour drug resistance pathways in order to pave the way for a more efffective cancer therapy.
Links with industry / industrial relevance (22)
By discovering new drugs able to block the uncontrolled growth in cancer cells, they could have a potential at commercial level.

Champ scientifique (EuroSciVoc)

Programme(s)

Thème(s)

Appel à propositions

Données non disponibles

Régime de financement

RGI - Research grants (individual fellowships)

Coordinateur

Imperial Cancer Research Fund
Contribution de l’UE
Aucune donnée
Adresse
44 Lincoln's Inn Fields
WC2A 3PX London
Royaume-Uni
Coût total
Aucune donnée