Mechanisms of co-existence of high levels of the PTEN and AKT protein in renal cell carcinoma

Objective To discuss the activity of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase (PI3K)/AKT pathway and the clinical significance of PTEN protein expression in clear-cell renal-cell carcinoma(CCRCC) tissues.Methods The protein of PTEN and AKT(phosphorylation at Ser473)of 36 paired CCRCC and adjacent non-neoplastic renal samples were analysed by Western-blot.The effect of PTEN on AKT activation was detected by Western-blot after transfected with si-RNA against PTEN in A-498 cell line.Results The significantly increased AKT(phosphorylation at Ser473)with decreased PTEN protein were observed in CCRCC tissues compared with the adjacent non-neoplastic renal samples while the PTEN protein expression had no significant association with pathological parameters.Blocking PTEN resulting in up-regulation of AKT phosphorylation.Conclusions Our findings indicate that as PTEN dominantly inhibits AKT activation,the coexistence of high levels of the PTEN protein with enhanced AKT activation suggests the existence of novel mechanisms which attenuate PTEN function in CCRCC.These mechanisms may reduce PTEN function or increase AKT activation.