GROWTH SUPPRESSION OF GLIOMA-CELLS BY PTEN REQUIRES A FUNCTIONAL PHOSPHATASE CATALYTIC DOMAIN

Deletions of all or part of chromosome 10 are the most common genetic alterations in high-grade gliomas, The PTEN gene (also called MMAC1 an d TEP1) maps to chromosome region 10q23 and has been implicated as a t arget of alteration in gliomas and also in other cancers such as those of the breast, prostate, and kidney, Here we sought to provide a func tional test of its candidacy as a growth suppressor in glioma cells, W e used a combination of Northern blot analysis, protein truncation ass ays, and sequence analysis to determine the types and frequency of PTE N mutations in glioma cell lines so that we could define appropriate r ecipients to assess the growth suppressive function of PTEN by gene tr ansfer, Introduction of wild-type PTEN into glioma cells containing en dogenous mutant alleles caused growth suppression, but was without eff ect in cells containing endogenous wild-type PTEN, The ectopic express ion of PTEN alleles, which carried mutations found in primary tumors a nd have been shown or are expected to inactivate its phosphatase activ ity, caused little growth suppression, These data strongly suggest tha t PTEN is a protein phosphatase that exhibits functional and specific growth-suppressing activity.