Induction of hRAD9 is required for G2/M checkpoint signal transduction in gastric cancer cells.
DNA damage triggers the activation of checkpoints that delay cell cycle progression to allow for DNA repair. Loss of G2 checkpoints provides a growth advantage for tumor cells undergoing aberrant mitosis. However, the precise mechanisms of G2 checkpoints acting in gastric cancer are unknown. Here, we analyzed the G2 checkpoint function in two gastric cancer cells, MKN-28 cells containing a mutant p53 gene and MKN-45 cells which have wild-type p53. Two agents damaging DNA, camptothecin (CPT) or ultraviolet light (UV), were utilized to trigger a G2 phase cell cycle checkpoint response in these tumor cells. Both CPT and UV inhibited the growth of MKN-45 cells, whereas they did not affect the growth of MKN-28 cells. CPT induced cell cycle arrest at the G2/M phase and enhanced the expression of human RAD9 (hRAD9) in MKN-45 cells. In addition, hRAD9 showed perinuclear staining and similar localization with Bcl-2 in MKN-45 cells but not in MKN-28 cells after having applied CPT or UV light. These results suggest that besides p53 activity, the induction of hRAD9 is required for G2/M checkpoint signal transduction in gastric cancer cells.
Hayashi
Ken
K
Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Kuniyasu
Hiroki
H
Oue
Naohide
N
Shigeishi
Hideo
H
Kuraoka
Kazuya
K
Nakayama
Hirofumi
H
Yasui
Wataru
W
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D004249:DNA Damage; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; C069930:rad9 protein; D002166:Camptothecin