Overexpressing (), a homolog of the human tumor suppressor gene , rescues the abnormal phenotype of the mutant.

One possible approach to normalize mutant cells that are metastatic and tumorigenic, is to upregulate a functionally similar homolog of the mutated gene. Here we have explored this hypothesis by generating an overexpressor of (), a homolog of , in mutants, the latter generated by targeted mutagenesis of a human epithelial cell line. Overexpression of normalized phenotypic changes associated with the PTEN mutation. The -associated changes rescued by overexpressing included 1) accelerated wound healing in the presence or absence of added growth factors (GFs), 2) increased division rates on a 2D substrate in the presence of GFs, 3) adhesion and viability on a 2D substrate in the absence of GFs, 4) viability in a 3D Matrigel model in the absence of GFs and substrate adhesion 5) loss of apoptosis-associated annexin V cell surface binding sites. The results justify further exploration into the possibility that upregulating by a drug may reverse metastatic and tumorigenic phenotypes mediated in part by a mutation in . This strategy may also be applicable to other tumorigenic mutations in which a homolog to the mutated gene is present and can substitute functionally.