Reduced expression of the Aα subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the Aα and Aβ 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 subdivided into 3 families, B, B' and B". It has been reported that the genes encoding the A alpha and B". subunits are mutated in various human cancers, suggesting that they may function as tumor suppressors. We investigated whether A alpha and A beta mutations occur in human gliomas. Using single strand conformational polymorphism analysis and DNA sequencing, 58 brain tumors were investigated, including 23 glioblastomas, 19 oligodendrogliomas and 16 anaplastic oligodendrogliomas. Only silent mutations were detected in the A alpha gene and no mutations in the A beta gene. However, in 43% of the tumors, the level of A alpha was reduced at least 10-fold. By comparison, the levels of the B alpha and C alpha subunits were mostly normal. Our data indicate that these tumors contain very low levels of core and holoenzyme and high amounts of unregulated catalytic C subunit. (C) 2001 Wiley-Liss, Inc.