Regulatory regions of growth-related genes can activate an exogenous gene of the alpha-fetoprotein promoter to a comparable degree in human hepatocellular carcinoma cells.
We examined the transcriptional activation by the regulatory regions of the midkine (MK), survivin (SUR), cyclooxygenase-2 (COX-2), telomerase reverse transcriptase (TERT) and alpha-fetoprotein (AFP) genes in human hepatocellular carcinoma cells. Luciferase assays showed that the SUR regulatory region exhibited the greatest activity and that the MK regulatory region activated the reporter gene better than the enhancer-linked AFP promoter even in high-AFP-producing cells. The COX-2 and TERT regulatory regions also activated the reporter gene better than the AFP enhancer/promoter in intermediate-AFP-producing cells. Combination of the regulatory regions arranged in tandem modulated their transcriptional activities, depending on the arrangement of the promoters and cells examined. These data suggested that the regulatory regions of the growth-related genes could be useful to activate a therapeutic gene in hepatocellular carcinoma cells irrespective of the amounts of AFP production but combinatory use of the promoter regions could not always contribute to enhanced activity.
Tomizawa
Minoru
M
Division of Pathology, Chiba Cancer Center Research Institute, Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan. nihminorcib@umin.ac.jp
Saisho
Hiromitsu
H
Tagawa
Masatoshi
M
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D051546:Cyclooxygenase 2; D016207:Cytokines; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics; D000078792:Midkine; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D000077022:Survivin; D019098:Telomerase / Q000235:genetics; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000235:genetics*
C107489:BIRC5 protein, human; D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D000509:alpha-Fetoproteins; D000078792:Midkine; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C509186:TERT protein, human; D019098:Telomerase