IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The DNA repair protein MSH2 inversely correlates with HSP27 expression in uterine cervical cancer
Autor/es:
DAIANA ALVAREZ-OLMEDO; MARTÍN ZOPPINO; SILVINA B. NADIN; MAYRA L. SOTTILE; MARIEL A. FANELLI; MARTÍN GUERRERO; DANIEL R. CIOCCA
Lugar:
Mendoza
Reunión:
Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2016
Institución organizadora:
Sociedad de Biología de Cuyo
Resumen:
The implication of HSP27 in DNA repair is still unclear. In mismatch repair system (MMR) we have recently demonstrated interactions between HSP27 and MMR proteins MLH1 and MSH2. The objective of this study was to evaluate the implications of HSP27 in DNA repair using database meta-analyses in uterine cervix carcinomas, and in HeLa tumor cells exposed to different cadmium (CdCl2) concentrations. Methodology: HeLa 1.3 (stable transfection control) and HeLa2.2 cells (HeLa stably downregulated for HSP27) were submitted to 0, 5, 50, 100 µM CdCl2 during 3 h and then allowed to recover in cadmium-free medium for 21 h. Viability was analyzed by MTT and Annexin V/IP. DNA damage/repair was evaluated by alkaline comet assay,γ-H2AX by immunofluorescence. The expression of MLH1, MSH2, MSH6 was tested by Western blot and by in-silico meta-analysis in TCGA database.Results: After recovery, viability was significantly reduced at 100 µM CdCl2(IC50) in both cell lines; but necrosis was dramatically triggered in HeLa 2.2. DNA damage increased specially in HeLa 1.3 cells after 3 h of Cd treatment; however both cellular lines were able to repair the damage. The expression of MSH2 and MSH6 was strongly affected by HSP27 levels, both were inversely related to HSP27 at the protein levels; additionally, database meta-analysis supported this findings for MSH2 mRNA(Pearson correlation -0,41; p value= 8.83x10-12). Conclusion: Our results showed that HSP27 affected the cell survival but not DNA repair. However, HSP27 may affect the DNA damage-recognition MMR orits regulation.