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Phenotypic analysis of human glioma cells expressing the MMAC1 tumor suppressor phosphatase

Oncogene volume 18, pages 1261–1266 (1999)Cite this article

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.

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Acknowledgements

We thank B Wu, C Young and J Sheung for generating purified recombinant MMAC1 protein. We would also like to thank J-H Her, A Mui, D Parry, M Tomlinson, D Woods, R Herbst and M McMahon for reagents and very helpful suggestions. The DNAX Research Institute is supported by the Schering-Plough Corporation.

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Author notes

  1. Joseph B Bolen

    Present address: Hoechst Marion Roussel, Oncology Disease Group, Route 202-206, PO Box 6800, Bridgewater, NJ, 08807, USA

Authors and Affiliations

  1. Department of Cell Signaling, DNAX Research Institute, Palo Alto, 94304, California, USA

    Alyssa M Morimoto, Amy E Berson, Gregory H Fujii & Joseph B Bolen

  2. Myriad Genetics, Inc., Salt Lake City, 84108, Utah, USA

    David H-F Teng & Sean V Tavtigian

  3. Canji Inc., San Diego, 92121, California, USA

    Robert Bookstein

  4. Department of Neuro-Oncology, MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Peter A Steck

Authors
  1. Alyssa M Morimoto
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  2. Amy E Berson
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  5. Sean V Tavtigian
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  6. Robert Bookstein
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  7. Peter A Steck
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Morimoto, A., Berson, A., Fujii, G. et al. Phenotypic analysis of human glioma cells expressing the MMAC1 tumor suppressor phosphatase. Oncogene 18, 1261–1266 (1999). https://doi.org/10.1038/sj.onc.1202441

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