Expression profile of Parkin isoforms in glioma

Parkin (PARK2) gene is involved in a wide variety of tumors, including glioma, the most common and lethal primary malignancy of the central nervous system. Inactivating somatic mutations and frequent intragenic deletions of PARK2 have been observed in human cancers. Furthermore parkin overexpression reduces glioma cells proliferation and analysis of its expression is predictive for the survival outcome of patients with glioma. To date, most studies have focused their attention on the role of the originally cloned parkin, ignoring the existence of other isoforms. In the present work we analyzed the expression pattern of parkin isoforms in astrocytomas of different grade (II, III, IV) and in various glioblastoma cell line. In all tumor samples were detected by immunoblotting using two different antibodies, bands of ~58, ~50 kDa and ~15 kDa, corresponding to H20, H1 and/or H5, H9 and/or H13 and/or H7 and/or H18 isoforms respectively. Furthermore their expression levels were higher in malignant glioblastoma than in less invasive gliomas indicating a correlation between the expression profile of parkin isoforms and tumor malignancy. To identify a comparable model for in vitro studies, their expression pattern has been also analyzed on immunoprecipitated of cell lysates from T98G, A172 and U87MG. These cells expressed H20, H1 and/or H5 and H3 and/or H12 isoforms as revealed by western blot analysis. These results suggest that the characterization of some PARK2 isoforms may be usefull clinically to develop a prognostic tool in patients with brain tumor