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

Abstract

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 (α and β) and the B subunit as multiple forms subdivided into 3 families, B, B′ and B″. It has been reported that the genes encoding the Aα and Aβ subunits are mutated in various human cancers, suggesting that they may function as tumor suppressors. We investigated whether Aα and Aβ 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 Aα gene and no mutations in the Aβ gene. However, in 43% of the tumors, the level of Aα was reduced at least 10‐fold. By comparison, the levels of the Bα and Cα 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.