Comparative analysis of DNA repair in stem and nonstem glioma cell cultures.
It has been reported that cancer stem cells may contribute to glioma radioresistance through preferential activation of the DNA damage checkpoint response and an increase in DNA repair capacity. We have examined DNA repair in five stem and nonstem glioma cell lines. The population doubling time was significantly increased in stem compared with nonstem cells, and enhanced activation of Chk1 and Chk2 kinases was observed in untreated CD133(+) compared with CD133(-) cells. Neither DNA base excision or single-strand break repair nor resolution of pH2AX nuclear foci were increased in CD133(+) compared with CD133(-) cells. We conclude that glioma stem cells display elongated cell cycle and enhanced basal activation of checkpoint proteins that might contribute to their radioresistance, whereas enhanced DNA repair is not a common feature of these cells.
Ropolo
Monica
M
Molecular Mutagenesis and DNA Repair Laboratory, Istituto Nazionale Ricerca Cancro, University of Genova, Genova, Italy.
Daga
Antonio
A
Griffero
Fabrizio
F
Foresta
Mara
M
Casartelli
Gianluigi
G
Zunino
Annalisa
A
Poggi
Alessandro
A
Cappelli
Enrico
E
Zona
Gianluigi
G
Spaziante
Renato
R
Corte
Giorgio
G
Frosina
Guido
G
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D017209:Apoptosis / Q000502:physiology; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair; D004789:Enzyme Activation; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D010455:Peptides / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; C578633:Chek2 protein, mouse; D017346:Protein Serine-Threonine Kinases