Reduced expression of the A alpha subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the A alpha and A beta subunit genes

Protein phosphatase 2A (PP2A) consists of 3 subunits: the catalytic subunit , C, and the regulatory subunits, A and B. The A and C subunits both exist as 2 isoforms (alpha and beta) and the B subunit as multiple forms subdivid ed into 3 families, B, B' and B". It has been reported that the genes encod ing the A alpha and B". subunits are mutated in various human cancers, sugg esting that they may function as tumor suppressors. We investigated whether A alpha and A beta mutations occur in human gliomas. Using single strand c onformational polymorphism analysis and DNA sequencing, 58 brain tumors wer e investigated, including 23 glioblastomas, 19 oligodendrogliomas and 16 an aplastic oligodendrogliomas. Only silent mutations were detected in the A a lpha gene and no mutations in the A beta gene. However, in 43% of the tumor s, the level of A alpha was reduced at least 10-fold. By comparison, the le vels of the B alpha and C alpha subunits were mostly normal. Our data indic ate that these tumors contain very low levels of core and holoenzyme and hi gh amounts of unregulated catalytic C subunit. (C) 2001 Wiley-Liss, Inc.