title: Active form of AKT controls cell proliferation and response to apoptosis in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. Deregulation of the AKT signaling pathway has been found in HCC. However, the effect of AKT activation on the proliferation and apoptosis in HCC is not clear. Herein, expression of phosphorylated form of AKT (Ser 473) was investigated in HCC tumor (n=73), cirrhosis (n=17), normal liver (n=22) samples and in HCC cell lines (n=8). The results showed that expression of p-AKT was higher in tumor (53%) than in cirrhotic tissues (12%) while it was absent in normal liver (p<0.0001). p-AKT expression was also associated with number of tumor nodules and differentiation status (p<0.05). LY294002 induced cell cycle arrest at G0/G1 in SNU-449 and Mahlavu cells by decreasing expression of CDK2, CDK4, CycD1, CycD3, CycE, CycA and increasing expression of p21 and p27 as well; it also caused a decrease in the E2F1 transcriptional activity through declining phosphorylated Rb. LY294002 did not affect the basal level of apoptosis; however, it amplified cisplatin-induced apoptosis in SNU-449 cells. When the p-AKT level was decreased specifically after transfection with the DN-AKT plasmid, SNU-449 cells became more sensitive to cisplatin-induced apoptosis. HuH-7 cells with no basal p-AKT, were markedly affected by the treatment of doxorubicin. Thus, Akt signaling controls growth and chemical-induced apoptosis in HCC and p-AKT may be a potential target for therapeutic interventions in HCC patients.
authors: Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir 35340, Turkey.
authors: Imge
authors: I
authors: Kunter
authors: Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir 35340, Turkey.
authors: Esra
authors: E
authors: Erdal
authors: Department of Pathology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors: Deniz
authors: D
authors: Nart
authors: Department of Pathology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors: Funda
authors: F
authors: Yilmaz
authors: Department of General Surgery, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir 35340, Turkey.
authors: Sedat
authors: S
authors: Karademir
authors: Department of Pathology, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir 35340, Turkey.
authors: Ozgul
authors: O
authors: Sagol
authors: Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Inciralti, Izmir 35340, Turkey.
authors: Nese
authors: N
authors: Atabey
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin