Dimethylsulfoxide (DMSO) has been known to differentiate HL60 cells into neutrophil like cells. Here, we provide an evidence for the involvement of tumor suppressor PTEN, an antagonist of phosphatidylinositol 3-kinase (PI3K) in the DMSO-induced differentiation of HL60 cells. DMSO upregulated PTEN with unaffecting the expression of PI3K. The upregulation of PTEN by DMSO lead to the decrease of Akt phosphorylation, a downstream of PI3K. The DMSO-induced upregulation of PTEN might be mediated by NF-KB activation, which was evidenced by the blockage of DMSO-induced PTEN upregulation with an NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC). (c) 2004 Elsevier Ltd. All rights reserved.