Proteomic analysis of an imatinib-resistant K562 cell line highlights opposing roles of heat shock cognate 70 and heat shock 70 proteins in resistance - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Proteomics Année : 2008

Proteomic analysis of an imatinib-resistant K562 cell line highlights opposing roles of heat shock cognate 70 and heat shock 70 proteins in resistance

Marion Pocaly
  • Fonction : Auteur
Valérie Lagarde
  • Fonction : Auteur
Gabriel Etienne
Maryse Dupouy
  • Fonction : Auteur
Delphine Lapaillerie
Stéphane Claverol
Sébastien Vilain
  • Fonction : Auteur
Marc Bonneu
  • Fonction : Auteur
François-Xavier Mahon
  • Fonction : Auteur
Jean-Max Pasquet
  • Fonction : Auteur

Résumé

Understanding the molecular basis of resistance to imatinib, a tyrosine kinase inhibitor used as front-line therapy in chronic myeloid leukemia, remains a challenge for successful treatment. In an attempt to identify new mechanisms of resistance, we performed a comparative proteomic analysis of an imatinib-resistant cell line generated from the erythroblastic cell line K562 (K562-r) for which no known mechanism of resistance has been detected. Bidimensional gel electrophoresis was carried out to compare the protein expression pattern of imatinib-sensitive and of imatinib-resistant K562 cells. Among the 400 matched spots on five pairs of gels, only 14 spots had a significantly increased or decreased expression leading to the identification of 24 proteins identified as scaffold proteins, metabolic enzymes, DNA translation and maturation, and chaperon proteins. Among the chaperon family, only Hsp70 and Hsc70 are overexpressed in K562-r, results confirmed by Western blotting. We recently reported the participation of Hsp70 overexpression in imatinib resistance whereas a role for Hsc70 has yet to be determined. Hsc70 is not involved in imatinib resistance as the inhibition of its expression by siRNA does not restore sensitivity to imatinib. In contrast, the induced decreased expression of Hsc70 was accompanied by a greater overexpression of Hsp70. This proteomic study therefore suggests opposing roles of Hsp70 and Hsc70 in imatinib resistance.

Domaines

Cancer

Dates et versions

hal-03155361 , version 1 (01-03-2021)

Identifiants

Citer

Marion Pocaly, Valérie Lagarde, Gabriel Etienne, Maryse Dupouy, Delphine Lapaillerie, et al.. Proteomic analysis of an imatinib-resistant K562 cell line highlights opposing roles of heat shock cognate 70 and heat shock 70 proteins in resistance. Proteomics, 2008, 8 (12), pp.2394-2406. ⟨10.1002/pmic.200701035⟩. ⟨hal-03155361⟩

Collections

CNRS
9 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More