RhoB role in the cellular mechanism of resistance to ionizing radiations
Description
Radiotherapy efficiency on cerebral tumors is limited by their poor sensitivity to ionizing radiation. Previous work in the laboratory have shown the role of the small GTPase RhoB and more specifically its farnesylated form in the cellular resistance to Ionizing radiation. The aim of this study is to elucidate cellular pathways leading to this protector effect. To do so we have over-expressed RhoB-F in a fibroblastic murine model sensitive to Ionizing radiation and also inhibited RhoB by RNA interference in radioresistant glioblastoma cells (U87). We demonstrate that RhoB induce a protector effect in this two cellular models controlling the mitotic cell death pathway, G2M arrest and over-duplication of the centrosomes all induced by Ionizing radiation. This work identify a new biological pathway controlling the tumoral radioresistance and could lead to the discovery of new inhibitors that could potentially increase the radiotherapy efficiency in clinical protocols. (author)
Abstract (French)
L'efficacite de la radiotherapie est limitee par la faible sensibilite des tumeurs cerebrales a l'irradiation. Les precedents travaux du laboratoire ont demontre l'implication de la petite GTPase, RhoB, et plus particulierement de sa forme farnesylee (RhoB-F) dans la radioresistance cellulaire. Le but de ce travail etait de decrypter les mecanismes cellulaires de cet effet radioprotecteur. Pour cela, nous avons successivement surexprime RhoB-F dans un modele de fibroblastes murins radiosensible NIH3T3 puis inhibe RhoB par des ARNi dans des cellules de glioblastomes radioresistantes U87. Nous demontrons que RhoB exerce son effet radioprotecteur dans ces deux modeles en controlant les mecanismes de mort mitotique, d'arret en G2/M et de surduplication des centrosomes radio-induits. Ce travail identifie donc une nouvelle voie biologique controlant la radioresistance tumorale et de nouvelles cibles pour des inhibiteurs susceptibles d'ameliorer l'efficacite de la radiotherapie en clinique. (auteur)Files
49089317.pdf
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Additional details
Additional titles
- Original title (French)
- Implication de RhoB dans les mecanismes cellulaires de reponse aux rayonnements ionisants
Publishing Information
- Imprint Pagination
- 138 p.
- Report number
- FRNC-TH--10219
INIS
- Country of Publication
- France
- Country of Input or Organization
- France
- INIS RN
- 49089317
- Subject category
- S63: RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; S62: RADIOLOGY AND NUCLEAR MEDICINE;
- Resource subtype / Literary indicator
- Thesis
- Quality check status
- Yes
- Descriptors DEI
- APOPTOSIS; ENZYME INHIBITORS; EXCISION REPAIR; FIBROBLASTS; GLIOMAS; GTP-ASES; MITOSIS; NECROSIS; RADIOPROTECTIVE SUBSTANCES; RADIOSENSITIVITY; RADIOTHERAPY; STRAND BREAKS; TRANSFERASES; TUMOR CELLS;
- Descriptors DEC
- ACID ANHYDRASES; ANIMAL CELLS; BIOLOGICAL RECOVERY; BIOLOGICAL REPAIR; CELL DIVISION; CONNECTIVE TISSUE CELLS; DISEASES; DNA DAMAGES; DNA REPAIR; DRUGS; ENZYMES; HYDROLASES; MEDICINE; NEOPLASMS; NERVOUS SYSTEM DISEASES; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; PATHOLOGICAL CHANGES; PROTEINS; RADIOLOGY; REPAIR; RESPONSE MODIFYING FACTORS; SENSITIVITY; SOMATIC CELLS; THERAPY;
Optional Information
- Notes
- [230 refs.]; Available from the INIS Liaison Officer for France, see the INIS website for current contact and E-mail addresses