Expression of bcl-2, bax and bcl-xl in human gliomas: A re-appraisal

We have analyzed the expression of the anti-apoptotic proteins bcl-2, bcl-x l and that of bax, a pro-apoptotic protein, in human WHO grade II astrocyto mas (LGA) and WHO grade IV glioblastoma multiforme (GBM). Tumors were obtai ned immediately after surgical resection and were analyzed by immunohistoch emistry (IHC), laser confocal microscopy (LCM) and immunoblots. Both IHC an d immunoblot analysis indicated that the expression of bcl-xl was not signi ficantly different between LGA and GBM. IHC indicated that the expression o f bcl-2 was inversely correlated to the grade of the tumors (i.e more cells were bcl-2 positive in LGA than in GBM) while the expression of bax was un affected by the grade of the tumor. In contrast, immunoblots revealed a par allel increase in the expression of bcl-2 and bax from the low to high grad e tumor, suggesting a co-regulation of the expression of these two proteins during tumoral progression. Confocal analyses provide us with another poss ible level of complexicity in the regulation of apoptosis in these tumors, as these markers exhibited different subcellular localizations: bcl-2 was s trictly associated with mitochondria and bcl-xl was present in both cytosol ic and mitochondrial compartments while bax was found essentially in the cy tosol of the tumoral cells. Taken together, our data suggest that the role of bcl-2 related proteins could be regulated at different levels in human a strocytomas (expression, subcellular localization, antigen exposure...) whi ch should be studied by different techniques.