IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
CANCER: MOLECULES IMPLICATED IN DNA REPAIR AND CELLULAR RESISTANCE
Autor/es:
ZOPPINO, FELIPE CARLOS MARTIN; GUERRERO GIMENEZ, MARTIN EDUARDO; NADIN, SB; FANELLI, MARIEL ANDREA; ALVAREZ-OLMEDO DAIANA; CIOCCA, DANIEL RAMON
Lugar:
Mendoza
Reunión:
Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2016
Institución organizadora:
Sociedad de Biología de Cuyo
Resumen:
Heat shock protein 27 (HSP27) is a molecular chaperone with numerous roles in cell functions. There is evidence pointing HSP27 as a key regulator in apoptosis, DNA repair and metastases, between others. In several cases, the overexpression of this protein is associated with drug resistance. This fact suggests that the downregulation of HSP27 could be a novel strategy for optimization of cancer treatment. Recently, we described an association between DNA repair proteins MLH1 and MSH2 and HSP27, but the implication of this interaction remains unclear. The DNA mismatch repair (MMR) system is necessary for the maintenance of the genomic stability which is important to avoid further transformation in cancer cells. Here we use database meta-analyses in uterine cervix carcinomas, and in HeLa tumor cells (wild type or downregulated for HSP27 expression), exposed to different cadmium (CdCl2) concentrations to unravel some of the biological function of HSP27 in the DNA repair. We evaluated the expression of MLH1, MSH2, MSH6 by immunoblotting in HeLa cells and by in-silico meta-analysis in TCGA database. Several biological parameters as viability, cellular death, DNA damage/repair and drug resistance were analyzed. The expression of MSH2 and MSH6 was strongly affected by HSP27 levels, and both were inversely related to HSP27 Additionally, database meta-analysis supported those findings for MSH2 mRNA (Pearson correlation -0,41; p value= 8.83x10-12). Conclusion: Our data indicate that the modulation of HSP27 affects the cell survival, but it might not affect DNA repair even when in cells were exposed to high Cd-concentrations. This could be explained by the interplay between DNA repair systems. In addition, we found an inverse correlation between HSP27 and MSH2, suggesting that HSP27 may affect the DNA damage recognition by MMR or its regulation.