Loss of cellular adhesion to matrix induces p53-independent expression of PTEN tumor suppressor

BACKGROUND: The tumor suppressor gene PTEN has been found mutated in many types of advanced tumors. When introduced into tumor cells that lack the wild-type allele of the gene, exogenous PTEN was able to suppress their ability to grow anchorage-independently, and thus reverted one of the typical characteristics of tumor cells. As these findings indicated that PTEN might be involved in the regulation of anchorage-dependent cell growth, we analyzed this aspect of PTEN function in non-tumor cells with an anchorage-dependent phenotype. RESULTS: We found that in response to the disruption of cell-matrix interactions, expression of endogenous PTEN was transcriptionally activated, and elevated levels of PTEN protein and activity were present in the cells. These events correlated with decreased phosphorylation of focal adhesion kinase, and occurred even in the absence of p53, a tumor suppressor protein and recently established stimulator of PTEN transcription. CONCLUSIONS: In view of PTEN's potent growth-inhibitory capacity, we conclude that its induction after cell-matrix disruptions contributes to the maintenance of the anchorage-dependent phenotype of normal cells.