Somatostatin analogs stimulate DNA-dependent protein kinase activity in human gastric tumoral cell-line HGT1.
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylates, in the presence of double-stranded DNA, several transcription-, replication- and repair -factors. Its interaction with the DNA-binding regulatory component Ku (p86-/p70-Ku) is required for stabilization and activity. We have previously shown that p86-Ku behaves as a specific receptor for the growth inhibitory tetradecapeptide, somatostatin. In this work, we investigate a possible regulation by somatostatin analogs, of DNA-PK activity in the human gastric tumoral HGT1/clone6 cell-line. We demonstrate that a 48 h-preincubation of cells with octreotide or RC-160, stimulates DNA-PK activity by 8 and 10 fold with ED50s of 1 and 0.1 nM, respectively. These stimulations appearing only after 3 h were inhibited by cycloheximide. They were not observed in a cell clone which was transfected by a cDNA encoding p86-Ku antisense. This study demonstrates the existence of a new somatostatin signaling pathway involving the stimulation of DNA-PK activity.
Sadji
Z
Z
Unité de Recherches Biologie et Pathologie de l'Epithélium Digestif, Inserm U10, Hôpital Bichat-Claude Bernard, IFR Cellules Epithéliales, Paris, France. zsadji@bichat.inserm.fr
Le Romancer
M
M
Hervatin
F
F
Lewin
M J
MJ
Reyl-Desmars
F
F
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002384:Catalysis; D002999:Clone Cells; D004265:DNA Helicases; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020319:Oligodeoxyribonucleotides, Antisense; C051458:vapreotide; D013004:Somatostatin; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D015282:Octreotide