PMID- 9356475 OWN - NLM STAT- MEDLINE DCOM- 19971216 LR - 20220311 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 94 IP - 23 DP - 1997 Nov 11 TI - Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domain. PG - 12479-84 AB - Deletions of all or part of chromosome 10 are the most common genetic alterations in high-grade gliomas. The PTEN gene (also called MMAC1 and TEP1) maps to chromosome region 10q23 and has been implicated as a target of alteration in gliomas and also in other cancers such as those of the breast, prostate, and kidney. Here we sought to provide a functional test of its candidacy as a growth suppressor in glioma cells. We used a combination of Northern blot analysis, protein truncation assays, and sequence analysis to determine the types and frequency of PTEN mutations in glioma cell lines so that we could define appropriate recipients to assess the growth suppressive function of PTEN by gene transfer. Introduction of wild-type PTEN into glioma cells containing endogenous mutant alleles caused growth suppression, but was without effect in cells containing endogenous wild-type PTEN. The ectopic expression of PTEN alleles, which carried mutations found in primary tumors and have been shown or are expected to inactivate its phosphatase activity, caused little growth suppression. These data strongly suggest that PTEN is a protein phosphatase that exhibits functional and specific growth-suppressing activity. FAU - Furnari, F B AU - Furnari FB AD - Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093-0660, USA. ffurnari@ucsd.edu FAU - Lin, H AU - Lin H FAU - Huang, H S AU - Huang HS FAU - Cavenee, W K AU - Cavenee WK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Tumor Suppressor Proteins) RN - EC 3.1.3.2 (Phosphoric Monoester Hydrolases) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) RN - EC 3.1.3.67 (PTEN protein, human) SB - IM MH - Brain Neoplasms/genetics/*pathology MH - Cell Division/genetics MH - *Chromosomes, Human, Pair 10 MH - *Gene Expression Regulation, Neoplastic MH - Glioma/*genetics/*pathology MH - Humans MH - Mutation MH - PTEN Phosphohydrolase MH - *Phosphoric Monoester Hydrolases MH - Protein Tyrosine Phosphatases/*genetics MH - Tumor Cells, Cultured MH - *Tumor Suppressor Proteins PMC - PMC25009 EDAT- 1997/11/14 00:00 MHDA- 1997/11/14 00:01 PMCR- 1998/05/11 CRDT- 1997/11/14 00:00 PHST- 1997/11/14 00:00 [pubmed] PHST- 1997/11/14 00:01 [medline] PHST- 1997/11/14 00:00 [entrez] PHST- 1998/05/11 00:00 [pmc-release] AID - 3016 [pii] AID - 10.1073/pnas.94.23.12479 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12479-84. doi: 10.1073/pnas.94.23.12479.