Preferential killing of PTEN-null myelomas by PI3K inhibitors through Akt pathway

摘要: We recently reported that internal deletion of PTEN tumor suppressor gene in OPM2 and Δ47 myeloma lines led to high Akt activation. Re-expression induced strong apoptosis growth inhibition. To understand the biologic importance phosphatidylinositol 3 kinase (PI3K)/Akt activation affected by deletion, we analysed inhibition applying PI3K inhibitors expressing constructs. The preferentially suppressed PTEN-null those PTEN, indicating is more critical for survival with mutations than others a functional gene. Since exhibited much stronger PTEN-expressing cells response insulin-like factor I stimulation, determined whether could be responsible PI3K-mediated cell lines. Expression an active Akt, but not its dead mutant, reversed wortmannin- dexamethasone-induced lines, suggesting lies downstream dexamethasone resistance. In summary, have provided evidence are stringently dependent on PI3K/Akt survival. These results may provide basis treat patients inhibitors.