Tumour suppressor PTEN regulates cell cycle and protein kinase B/Akt pathway in breast cancer cells.

BACKGROUND

PTEN is a tumour suppressor protein with phosphatase activity frequently altered in several types of human cancers.

MATERIALS AND METHODS

The PTEN effect was studied on the cell cycle (by bromdeoxyuridine incorporation) and on the phosphatidylinositol-3-kinase/protein kinase B/Akt (PI3-K/PKB/Akt) pathway regulating proteins (by immunocytochemical, Western blot analysis and kinase assay) upon transfection of wild-type PTEN and its mutant H123Y in breast cancer cell lines.

RESULTS

The expression of the important proteins in the MCF-7 and BT-549 cells was characterised and the cellular localisation of PTEN was analysed. Transfection of H123Y led to the down-regulation of p27(Kip1) and p21(Waf1/Cip1) protein levels and the up-regulation of phosphorylated PKB/Akt. An overexpression of PTEN decreased cyclin E/cdk2 activity and inhibited S-phase entry in MCF-7. In BT-549 these changes were not observed, but overexpression of PTEN led to a diminution of PKB/Akt phosphorylation.

CONCLUSION

PTEN function is mediated through the inhibition of the cell cycle and PKB/Akt phosphorylation in breast cancer cells.