The phosphatidylinositol 3-kinase/Akt pathway regulates the HCCR-1 oncogene expression.
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.
Cho
Goang-Won
GW
Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, 137-040, Republic of Korea.
Shin
Seung Min
SM
Namkoong
Hong
H
Kim
Hyun Kee
HK
Ha
Seon-Ah
SA
Hur
Soo Young
SY
Kim
Tae Eung
TE
Chai
Young-Gyu
YG
Kim
Jin Woo
JW
D024506:5' Flanking Region; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
C516325:HCCR1 protein, mouse; C476732:LETMD1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt