RT Journal Article
SR Electronic
T1 The effect of compensatory induction of various PTEN mutants against TGFβ-induced translocation of β-catenin in lung cancer cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P522
VO 42
IS Suppl 57
A1 Masaaki Kusunose
A1 Naozumi Hashimoto
A1 Daisuke Aoyama
A1 Yoshinori Hasegawa
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P522.abstract
AB BackgroundTransforming growth factor β(TGFβ)-induced β-catenin translocation into cytoplasm is involved in epithelial-mesenchymaltransition(EMT). In this congress, we also show that modulation of phosphorylation sites in the PTEN C-terminus (PTEN4A) inhibits TGFβ-induced EMT via blockade of β-catenin translocation. Nevertheless, how PTEN4A could exert the inhibitory effect on β-catenin translocation remains elusive.ObjectivesWe aimed to illuminate the underlying mechanisms, by using several PTEN constructs with deletion mutants.MethodsWe prepared four deletion mutants with the phosphatase domain, the C2 domain, and/or the PTEN C-terminus. Thus, we established lung cancer cells with a Dox-dependent gene expression system, in which these mutants were induced only when Dox is added. To evaluate the localization of β-catenin, immunofluorescence and confocal laser scanning microscopy were performed.ResultsImmunofluorescence images suggested that the PTEN C-terminus did not appear to directly inhibit TGFβ-induced β-catenin translocation into cytoplasm. We showed that the phosphatase domain might be important to block the β-catenin translocation.ConclusionsInhibition of phosphorylation of the PTEN C-terminus, by which the phosphatase domain could retain the PTEN phosphatase activity, might blunt TGFβ-induced β-catenin translocation as well as EMT.