Role of HSP27 (HSPB1) phosphorylation on MSH2 related to cancer progression in glioma cells: preliminary results.

GISELA N. CASTRO, NIUBYS CAYADO GUTIÉRREZ, NATALIA L. LEIVA, FELIPE C. M. ZOPPINO, MARTÍN E. GUERRERO, DANIEL R. CIOCCA.

Huangshan

Congreso; Seventh International Congress on Stress Response in Biology and Medicine; 2015

International Cell Stress Society

Temozolomide (TMZ) is the main drug administrated to patients suffering of high grade gliomas. These tumors are highly invasive and lethal. Although many therapeutic approaches have been explored, there has been no major improvement in survival over the last years. In a previous study in human gliomas we reported that heat shock proteins (HSPs) HSP27 and HSPA together with β-catenin, P53, and MGMT were associated with high-grade astrocitomas, suggesting that these markers are related with the disease outcome and the response to treatments. The MMR system include MSH2 protein and MGMT enzyme are responsible for repairing the DNA damages induced by TMZ. We have recently reported that HSP27 and MSH2 co-localized in Gli36 cells in absence of the drug, and this co-localization was significantly increased after TMZ; the immunoprecipitation studies supported the interaction between both proteins.Tumor recurrence and resistance to TMZ remain major challenges in malignant gliomas, so it is necessary to explore the molecular mechanisms of resistance/ susceptibility associated to treatment. In the present study we have examined the role of HSP27 phosphorylation (p-HSP27) on MSH2 expression in glioma cells.Las 3 líneas celulares presentaron diferencias en la viabilidad, apoptosis y senescencia luego del tratamiento con TMZ. En la línea celular Gli36 se encontró una colocalización nuclear de las proteínas MSH2 y HSPB1 que aumenta luego de la administración de TMZ. Se demostró por primera vez que HSPB1 interactúa con MSH2 en una línea celular de glioma.