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

MMAC1, also known as PTEN or TEP-1, was recently identified as a gene commo nly mutated in a variety of human neoplasias, Sequence analysis revealed th at MMAC1 harbored sequences similar to those found in several protein phosp hatases, Subsequent studies demonstrated that MMAC1 possessed in vitro enzy matic activity similar to that exhibited by dual specificity phosphatases, To characterize the potential cellular functions of MMAC1, we expressed wil d-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 dens ity, expression of enzymatically inactive MMAC1 significantly enhanced grow th in soft agar, Our observations indicate that while wild-type MMAC1 exhib its activities compatible with its proposed role as a tumor suppressor, cel lular expression of MMAC1 containing mutations in the catalytic domain may yield protein products that enhance transformation characteristics.