The phosphatidylinositol 3-kinase/Akt pathway regulates the HCCR-1 oncogene expression

• Published in: Gene 2006-12, Vol.384, p.18-26
• Main Authors: Cho, Goang-Won, Shin, Seung Min, Namkoong, Hong, Kim, Hyun Kee, Ha, Seon-Ah, Hur, Soo Young, Kim, Tae Eung, Chai, Young-Gyu, Kim, Jin Woo
• Format: Article
• Language: English
• Subjects: 5' Flanking Region; Animals; Base Sequence; Cell Line; Cell Line, Tumor; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Homeodomain; Human cancer; Humans; K562; LY-294002; Mice; Molecular Sequence Data; NIH 3T3 Cells; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Promoter; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Signal Transduction
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2006.07.006

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.