The expression and the nuclear activity of the caretaker gene ku86 are modulated by somatostatin.
Somatostatin is a peptide hormone that exerts antisecretory and antiproliferative activities on some human tumors. The Ku70/86 heterodimer acts as regulatory subunit of the DNA dependent protein kinase and its DNA binding activity mediates DNA double strands breaks repair that is crucial to maintain the genetic integrity of the genome. The activation of the heterodimer regulates cell cycle progression and the activity of nuclear transcription factors involved in DNA replication and cell proliferation. Moreover Ku86 behaves as a receptor for the growth inhibitory tetradecapeptide, somatostatin. Herein we report that somatostatin treatment to a colon carcinoma cell line (Caco-2) inhibits cell growth and, at same time, strongly modulates the activation of Ku70/86 heterodimer and the levels of Ku86 in the nucleus by increasing its specific mRNA level. Our findings are consistent with the hypothesis that somatostatin controls cell cycle progression and DNA repair through a new signalling pathway that involves the regulation of Ku86 level and modulates the Ku70/86 activity in the nucleus.
Pucci
S
S
Dept. of Biopathology, University of Rome "Tor Vergata", via Montpellier 1, 00133 Rome, Italy.
Bonanno
E
E
Pichiorri
F
F
Mazzarelli
P
P
Spagnoli
L G
LG
D034961:Antigens, Nuclear / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013004:Somatostatin / Q000494:pharmacology*
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D013004:Somatostatin; D004247:DNA; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen