The human cervical cancer oncogene HCCR-1 is overexpressed in various human cancers, and might function as a negative regulator of the p53 tumor suppressor. To determine the regulatory pathway involved in the HCCR-1 gene expression, we searched the 5' flanking region of HCCR-1 and identified HCCR-1 promoter including putative homeodomain protein binding sites. The level of HCCR-1 expression was increased during the mouse embryogenesis. Expression of phosphatidylinositol 3-kinase (PI3K) in NIH/3T3 cells activated the HCCR-1 promoter. This promoter was also activated by wild type Akt but not by dominant negative Akt in K562 cells. In addition, the level of HCCR-1 was decreased by PI3K inhibitor, LY-294002, in a dose dependent manner. Northern blot analysis revealed that the HCCR-1 gene expression was down-regulated by LY-294002. These results suggest that the HCCR-1 oncogene expression was regulated by the PI3K/Akt signaling pathway.