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TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells
- Source :
- Cancer letters. 279(1)
- Publication Year :
- 2008
-
Abstract
- TRAP1 is a component of a pro-survival mitochondrial pathway up-regulated in tumor cells. The evaluation of TRAP1 expression in 26 human colorectal carcinomas showed up-regulation in 17/26 tumors. Accordingly, TRAP1 levels were increased in HT-29 colorectal carcinoma cells resistant to 5-fluorouracil, oxaliplatin and irinotecan. Thus, we investigated the role of TRAP1 in multi-drug resistance in human colorectal cancer. Interestingly, TRAP1 overexpression leads to 5-fluorouracil-, oxaliplatin- and irinotecan-resistant phenotypes in different neoplastic cells. Conversely, the inhibition of TRAP1 activity by TRAP1 ATPase antagonist, shepherdin, increased the sensitivity to oxaliplatin and irinotecan in colorectal carcinoma cells resistant to the single agents. These results suggest that the increased expression of TRAP1 could be part of a pro-survival pathway responsible for multi-drug resistance. © 2009 Elsevier Ireland Ltd. All rights reserved.
- Subjects :
- Oncology
Male
Cancer Research
medicine.medical_specialty
Genotype
Organoplatinum Compounds
Colorectal cancer
medicine.medical_treatment
Antineoplastic Agents
Apoptosis
Drug resistance
Mouse model of colorectal and intestinal cancer
Irinotecan
Transfection
Internal medicine
medicine
Humans
HSP90 Heat-Shock Proteins
RNA, Messenger
Aged
Aged, 80 and over
Chemotherapy
Dose-Response Relationship, Drug
Chemistry
Carcinoma
Middle Aged
medicine.disease
Phenotype
digestive system diseases
Drug Resistance, Multiple
Peptide Fragments
Oxaliplatin
Mitochondria
Up-Regulation
Gene Expression Regulation, Neoplastic
Drug Resistance, Neoplasm
Cancer research
Camptothecin
Female
Fluorouracil
Colorectal Neoplasms
HT29 Cells
medicine.drug
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 279
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....bf8b8d5db26fff7e1e9de13a93effe44