IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
HSP27 affects DNA damage response in human colon cancer cells treated with cisplatin
Autor/es:
LOSSINO A.D.; VARGAS ROIG LM; REDONDO AL; NADIN SB; VILCHEZ ARUANI J; FANELLI MA
Lugar:
San Luis
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 (P