[Influence of PKB on ROS regulation of proliferation in human 7721 hepatoma cells].
In the present study, the relationship between PKB signaling and reactive oxygen species (ROS) during the course of exogenous and endogenous ROS or antioxidants regulating human 7721 hepatoma cell proliferation was studied. To change endogenous ROS levels, 7721 cells were transfected with human manganese superoxide dismutase (MnSOD) construct containing sense or antisense MnSOD cDNA. Low level of exogenous ROS H2O2(1-10 mumol/L) significantly stimulated PKB activity and c-fos/c-jun expression and cell growth, which could be abolished by antioxidant danshensu (40 mg/L). It was observed that overexpression of MnSOD inhibited 7721 cell growth by inhibiting PKB activity and c-fos/c-jun expression; the PKB activity and c-fos/c-jun expression, however, were stimulated by down-regulated MnSOD expression. In addition, PKB-7721 cells (transfected with sense PKB cDNA) promoted c-fos/c-jun expression by stimulating PKB activity. These results suggest that the redox state stimulated hepatoma cell growth through PKB pathway, which modulates AP-1 expression.
Liu
Shan-Lin
SL
Department of Biochemistry, Medical Center of Fudan University, Shanghai 200032, China. slliu@shmu.edu.cn
Liu
Guan-Zhong
GZ
Cheng
Jian
J
Shi
Dong-Yun
DY
Chen
Hui-Li
HL
Zhang
Ya-Dong
YD
D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D013482:Superoxide Dismutase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt