%0 Journal Article
%T Loss of cellular adhesion to matrix induces p53-independent expression of PTEN tumor suppressor
%A Ray-Chang Wu
%A Martina Blumenthal
%A Xinwei Li
%A Axel H Sch£¿nthal
%J BMC Molecular Biology
%D 2002
%I BioMed Central
%R 10.1186/1471-2199-3-11
%X 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.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.The tumor suppressor gene PTEN (also called MMAC1) has been found deleted or mutated in a great variety of human tumors and tumor cell lines [1-3], and its tumor suppressing function has been confirmed in several in vitro studies [4-10]. Mice which are homozygously deficient in wild-type PTEN die during embryonic development and harbor regions of increased cellular proliferation, whereas heterozygous mice are viable but spontaneously develop tumors of various origins [11,12].PTEN has been shown to exhibit dual specificity protein phosphatase activity, as well as lipid phosphatase activity in vitro[13-18]. These enzymatic functions appear to be involved in the regulation of at least two separate signal transduction pathways. First, PTEN's protein phosphatase activity is able to down-regulate focal adhesion kinase (FAK) phosphorylation, which leads to the inactivation of the Ras/MAP kinase pathway [19-21]. Second, its lipid phosphatase activity targets the second messenger phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and thereby blocks activation of the protein kinase B (PKB/Akt) pathway [11,18,22-24]. Whereas both of the above pathways are intimately involved in the control of cell growth and survival, PTEN-regulated FAK activity further appears to impinge on cell adhesion, cell migration, and cell invasion [20,21]. It therefore emerges that the lo
%K Tumor Suppressor
%K PTEN
%K Anchorage-dependence
%K p53
%K Adhesion
%U http://www.biomedcentral.com/1471-2199/3/11