The human GSTP1 gene is frequently up-regulated in human malignancies and is associated with resistance to chemotherapy and an aggressive biology. Presently, however, the molecular mechanisms involved in the regulation of this gene are not well understood. We report here the transcriptional activation of the human GSTP1 gene by the second messenger, cAMP, in human tumor cells and provide evidence that this occurs via a CRE and the AP-1 site in the 5′-regulatory region of the GSTP1 gene. The data support cAMP signaling pathways in mechanisms of GSTP1 gene regulation. © 2001 Elsevier Science Ireland Ltd. All rights reserved.