Role of HSPB1 phosphorylation on MSH2 and proteins related to cancer progression in glioma cells: Preliminary results.

GISELA N CASTRO, NIUBYS CAYADO-GUTIÉRREZ, LEIVA NATALIA, FELIPE C. M. ZOPPINO, MARIEL A. FANELLI, F. DARÍO CUELLO-CARRIÓN, MARTÍN E. GUERRERO, DANIEL R. CIOCCA

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

Cell Stress Society International

Role of HSPB1 (HSP27) Phosphorylation on MSH2 and Proteins Related to Cancer Progression in Glioma Cells: Preliminary Results.Aim: Temozolomide (TMZ) is the main drug administrated to patients suffering from high-grade gliomas; however tumor recurrence and drug resistance remain major challenges. We have recently reported that HSPB1 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. In the present study we have examined the role of HSPB1 phosphorylation (p-HSPB1) on MSH2 levels and its relation with proteins associated to tumor progression. Methods: Gli36 cells were transfected with HSPB1 plasmids including mutants in which the phosphorylatable serine residues have been replaced by aspartate to mimic the phosphorylated protein, or alanine to mimic the non-phosphorylated protein, and HSPB1 wild type. The proteins were evaluated by immunofluorescence and immunoblotting. Results: We found HSPB1 overexpression in wild type and phosphorylated forms after transfection. HSPB1 phosphorylation appeared associated to a significant increase of MSH2 levels. These effects were further amplified after TMZ administration. Other proteins related to tumor progression and DNA repair are being examined. Conclusion: This is the first study that reports the role of p-HSPB1 after TMZ administration in human glioma cells.