29. MnSOD in brain primitive tumors

The antioxidant enzyme MnSOD has been found modified in human neoplasms in correlation with tumor differentiation. To address the issue of its role in tumor transformation and progression, we evaluated the content of this enzyme in 49 primitive brain tumors with different degree of differentiation (WHO grade II-IV), by means of Western blot and immunohistology. Our results show that immunoreactive MnSOD increases in a direct relationship with tumor grade and is inversely correlated with differentiation. The increase is specific to brain glial tumors. Glioblastomas have a profile characterized by a double peak, since 10/25 show "low" levels of immunoreactive protein which seem to correlate with a better prognosis. Several reports have hypothesized a possible role of reactive oxygen species as possible second messengers in the transduction of proliferative signaling initiated by phosphotyrosine kinase receptors. In order to explore the hypothesis that redox state can influence the signaling cascade, we have analyzed the subgroup of glioblastomas that show the double peak of MnSOD expression. We evaluated MAPK expression and the phosphorilation of a 42 KD band showing the same electrophoretic mobility of MAPK. Preliminary results show that MAPK is expressed and activated in most of grade IV tumors. The subgroup of low expression MnSOD tumors presents a reduced expression and activation of p42. A larger series will allow to clarify the relationship between MnSOD expression and activation of the signaling cascade.