PERSONAL DE APOYO
VILCHEZ ARUANI Juan
congresos y reuniones científicas
Título:
HSP27 AFECTA LA RESPUESTA AL DAÑO AL ADN EN CÉLULAS TUMORALES DE COLON HUMANO TRATADAS CON CISPLATINO
Autor/es:
VILCHEZ ARUANI, JUAN; LOSSINO, ANTONELLA; REDONDO, ANALÍA; FANELLI, MARIEL; VARGAS ROIG, LAURA; NADIN, SILVINA
Lugar:
Mendoza
Reunión:
Congreso; XXXVII Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2019
Institución organizadora:
Sociedad de Biología de Cuyo
Resumen:
HSP27 (HSPB1) belongs to the heat shock protein family with fundamental roles in protein homeostasis, transport processes and signal transduction. HSP27 as an anti-apoptotic protein is over-expressed in many cancer cells. It has been also involved in cancer progression, resistance to cancer therapy and prognosis. Accordingly, HSP27 has become an attractive therapeutic target. Previously, we reported that HSP27 interacts with DNA mismatch repair proteins especially after cisplatin (cPt) treatment. However, the role of HSP27 in the response to cPt-induced DNA damage through ATR-CHK1 pathway in mismatch repair (MMR) proficient/deficient tumor cells remains unknown. Here, using cultured human colon cancer cell lines HCT116+ch2 (MMR deficient, MMR-) and HCT116+ch3 (MMR proficient, MMR+) exposed to 10 μM of cPt for 24 h, we explored the DNA damage by comet assay and the expression of phosphorylated CHK1 (pCHK1, Ser345), γH2AX and pHSP27 (Ser78) by western blot. Cells were collected at T0 (immediately after cPt treatment), T3, T9 and T24 (3, 9 and 24 hs post-cPt). Downregulation of HSP27 was obtained using the antisense oligonucleotide (OGX427) in a group of cells before cPt exposure. HSP27 expression was reduced by 50% by OGX427. After cPt treatment, HSP27 and γH2AX expression increased progressively from T0 to T24 in MMR- cells; but MMR+ cells showed constant expression levels of HSP27 and increased levels of γH2AX with a significant peak at T3 (P0.6 at T3 and >0.8 at T9; and MOC2 >0.7 at T3 and T9. No significant differences in the colocalization coefficients were found between both cell lines. Our preliminary data indicate that HSP27 might be involved in the DNA damage response associated with cPt treatment through CHK1 pathway. Downregulation of HSP27 by OGX427 affects the levels of DNA damage and pCHK1 especially in MMR proficient tumor cells. Further studies will be needed to establish HSP27 effects on cPt sensitivity upstream or downstream the kinase CHK1.