IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
HSPB1 and HSPA1A associate with Mismatch Repair proteins in human colon cancer cell lines
Autor/es:
M.L. SOTTILE; A.D. LOSSINO; M.A. FANELLI; F.D. CUELLO CARRIÓN; L.M. VARGAS-ROIG; S.B. NADIN
Lugar:
Montevideo
Reunión:
Conferencia; First conference of the South American chapter of Cell Stress Society International; 2014
Institución organizadora:
Cell Stress Society International
Resumen:
Heat shock proteins (HSPs) are involved in the regulation of proteostasis. Among them, HSPB1 and HSPA1A can promote cell survival, in part by their ability to inhibit apoptosis. There is increasing evidence that HSPs participate in DNA repair mechanisms. Cisplatin is a widely used anticancer agent and resistance to the drug has been related with Mismatch Repair (MMR) deficiency. MMR protein complexes (MSH2/MSH6, MLH1/PMS2) are able to bind cisplatin-DNA adducts, but instead of increasing cell viability, MMR is important for drug-mediated cytotoxicity. At present, little is known about the relationship between HSPs and MMR system. The aims of our study were to characterize effects of cisplatin and hyperthermia on cell viability, HSPB1, HSPA1A, HSF1, MLH1, MSH2, ERCC1 proteins expression and to demonstrate associations between HSPs and MMR proteins. Human colon cancer cell lines: HCT116, HCT116+ch2 (MLH1-deficients, MMR-) and HCT116+ch3 (MLH1-proficient, MMR+) were used. Cells were exposed to cisplatin (cPt) or hyperthermia before cisplatin (H+cPt). cPt induced HSF1 expression 24 h after treatment, but did not affect HSPB1 expression in MMR+ cells. In contrast, HSF1 levels were not modified by cPt in MMR- cells. As expected, thermal treatment before cPt induced HSF1 and HSPs expression in MMR-/+ cells. Hyperthermia reduced MSH2 and ERCC1 expressions, and cell viability in MMR- cells. The heat stress also reduced MSH2, ERCC1 and MLH1 expressions in MMR+ cells, and cell survival 24 h post-cPt. Pearson colocalization coefficient revealed that HSPs and MMR proteins colocalized and these associations resulted higher in cPt- than in H+cPt-treated MMR+ cells (P