Response of glioma cells to temozolomide (TMZ) administration, effects on proteins implicated in the protection of their genome integrity

CASTRO G. N.; CAYADO-GUTIÉRREZ N.; NADIN S. B.; FANELLI M. A.; CUELLO CARRION F. D.; CIOCCA D. R.

Sheffield

Congreso; VI International Congress on Stress Proteins in Biology and Medicine; 2013

Cell Stress Society International

In human gliomas we detected that HSP27 and HSP70 together with beta-catenin, p53, and O(6)-methylguanine DNA methyltransferase (MGMT) were associated with high-grade astrocitomas. In addition, in oligodendroglial tumors HSP27 appeared as a surrogate molecular marker of loss of heterozygosity of 1p. We have now studied in human glioma cel lines the effects of TMZ on the cell survival and on the expression levels of proteins implicated in DNA repair, with the aim to identify if these proteins can be molecular targets when the cells display TMZ resistance. TMZ is the main drug administrated to patients suffering of high grade gliomas, the promoter methylation status of MGMT is used to guide this treatment. The three cell lines exhibited different cell survival, apoptosis, senescence and capacity to form colonies. In Gli36 cells, TMZ induced no senescence, high DNA damage (comet assay) and low long-term survival; however, they maintained their viability (MTT assay). In these cells TMZ increased MGMT, HSP27 and MLH1 levels. In contrast, MSH2 remained stable during TMZ treatment, this protein appeared in the nuclei (similar to what happens with HSP27). In co-immunoprecipitation studies MSH2 and HSP27 appeared interacting. We will present the characterization of these molecular mechanisms that appearas implicated in the resistance of glioma cells to anticancer treatment.