A P53 target gene, PIG11, contributes to chemosensitivity of cells to arsenic trioxide.
The tumor suppressor p53 regulates the expression of various genes that promote apoptosis. PIG11 (P53-induced gene 11), also referred to as TP53I11 (tumor protein p53 inducible protein 11), is a direct p53 target gene. Recent data demonstrated that PIG11 was up-regulated markedly in arsenic trioxide induced apoptosis by DDRT-PCR, suggesting a new class of p53 target genes that sensitize cells to the effects of chemotherapeutic agents. In this study, through the construction of a recombinant GFP-PIG11 expression vector and transfection of HEK293 cells with GFP or GFP-PIG11, the role of PIG11 in apoptosis was analyzed. Results demonstrated that the percentage (11.38%) of apoptotic cells with GFP-PIG11 transfection was higher than that (7.28%) of with only GFP transfection (P<0.05). At 24 h after 1 microM of arsenic trioxide treatment, apoptotic cells exhibited a significant increase in the expression of GFP-PIG11 (36.67%+/-2.78), in contrast, 10.50%+/-2.03 only GFP and 5.25%+/-0.96 vehicle control (P<0.01). In addition, we showed that intracellular content of reactive oxygen species (ROS) was 9.66+/-0.52 in GFP-PIG11 transfection, higher than 5.21+/-0.08 in GFP only and 5.99+/-0.45 in vehicle control (P<0.01). The above results suggest that overexpression of PIG11 could induce cell apoptosis in the low levels and enhanced the apoptotic effects of arsenic trioxide. The process could be involved in intracellular generation of ROS.
Liang
Xiao-Qiu
XQ
Institute of Biophysics, Academia Sinica, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Cao
En-Hua
EH
Zhang
Yan
Y
Qin
Jing-Fen
JF
D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001483:Base Sequence; D002460:Cell Line; D016384:Consensus Sequence; D005786:Gene Expression Regulation / Q000502:physiology*; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007668:Kidney; D009363:Neoplasm Proteins; D010087:Oxides / Q000633:toxicity*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D001152:Arsenicals; D009363:Neoplasm Proteins; D010087:Oxides; D011506:Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C483846:TP53I11 protein, human; D000077237:Arsenic Trioxide