Activation of activator protein 1 and extracellular signal-regulated kinases in human hepatocellular transformation.
Hepatocellular carcinoma is one of the most common tumors worldwide. Activator protein 1 (AP-1) is a nuclear transcription factor, and its transactivation is required for transformation in several cell lines. However, no direct correlation between AP-1 activity and human hepatocellular transformation has been proved. Here we analyzed the role of AP-1 on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced human hepatocellular transformation. TPA promoted the formation of anchorage-independent colonies, induced the AP-1 activity, and enhanced the DNA-binding ability of AP-1 in human hepatocytes. The phosphorylation of extracellular signal-regulated protein kinases (ERKs) was increased by TPA and the TPA-induced AP-1 activity was inhibited by PD98059, indicating that TPA-induced AP-1 activation was via ERK pathway. Moreover, retinoic acid and PD98059, which inhibited the AP-1 activity, abolished the TPA-induced transformation. Our findings indicated that AP-1 and ERKs activations were required for TPA-induced human hepatocellular transformation. These studies suggested that AP-1 could be the target for the development of antihepatocellular transformation agents.
Hsiang
Chien-Yun
CY
Department of Microbiology, China Medical University, Taichung 404, Taiwan.
Wu
Shih-Lu
SL
Ho
Tin-Yun
TY
D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D010703:Phorbol Esters / Q000008:administration & dosage / Q000633:toxicity; D010766:Phosphorylation; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010703:Phorbol Esters; D018808:Transcription Factor AP-1; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases