Phenotypic analysis of human glioma cells expressing the MMAC1 tumor suppressor phosphatase
- 11 February 1999
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 18 (6) , 1261-1266
- https://doi.org/10.1038/sj.onc.1202441
Abstract
MMAC1, also known as PTEN or TEP-1, was recently identified as a gene commonly mutated in a variety of human neoplasias. Sequence analysis revealed that MMAC1 harbored sequences similar to those found in several protein phosphatases. Subsequent studies demonstrated that MMAC1 possessed in vitro enzymatic activity similar to that exhibited by dual specificity phosphatases. To characterize the potential cellular functions of MMAC1, we expressed wild-type and several mutant variants of MMAC1 in the human glioma cell line, U373, that lacks endogenous expression. While expression of wild-type MMAC1 in these cells significantly reduced their growth rate and saturation density, expression of enzymatically inactive MMAC1 significantly enhanced growth in soft agar. Our observations indicate that while wild-type MMAC1 exhibits activities compatible with its proposed role as a tumor suppressor, cellular expression of MMAC1 containing mutations in the catalytic domain may yield protein products that enhance transformation characteristics.Keywords
This publication has 16 references indexed in Scilit:
- Phosphorylation and Activation of p70 s6k by PDK1Science, 1998
- Growth suppression of glioma cells by PTEN requires a functional phosphatase catalytic domainProceedings of the National Academy of Sciences, 1997
- PTEN1 is frequently mutated in primary endometrial carcinomasNature Genetics, 1997
- Germline mutations in PTEN are present in Bannayan-Zonana syndromeNature Genetics, 1997
- Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndromeNature Genetics, 1997
- Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancersNature Genetics, 1997
- PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate CancerScience, 1997
- Cell-cycle control linked to extracellular environment by MAP kinase pathway in fission yeastNature, 1995
- MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivoCell, 1993
- Efficient retroviral-mediated gene transfer into human B lymphoblastoid cells expressing mouse ecotropic viral receptorNucleic Acids Research, 1992