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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

✍ Scribed by Stefano Colella; Hiroko Ohgaki; Ralf Ruediger; Fan Yang; Mitsutoshi Nakamura; Hironori Fujisawa; Paul Kleihues; Gernot Walter

Publisher
John Wiley and Sons
Year
2001
Tongue
French
Weight
161 KB
Volume
93
Category
Article
ISSN
0020-7136

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✦ Synopsis

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 (␣ and ␤) 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␣ and A␤ subunits are mutated in various human cancers, suggesting that they may function as tumor suppressors. We investigated whether A␣ and A␤ 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␣ gene and no mutations in the A␤ gene. However, in 43% of the tumors, the level of A␣ was reduced at least 10-fold. By comparison, the levels of the B␣ and C␣ 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.

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