Overexpression of Sp1 leads to p53-dependent apoptosis in cancer cells.
Numerous studies have documented that Sp1 expression level were elevated in various human cancers. However, the promoters of many pro-apoptotic genes have been found to contain the Sp1 binding elements and are activated by Sp1 overexpression. To better understand the role and the mechanism of increased Sp1 levels on apoptosis, we used adenovirus to ectopically express GFP-Sp1 protein in various cancer cell lines. First, in HeLa and A549 cells, we found that Sp1 overexpression suppressed the cell growth and increased the detection of sub-G1 fraction, caspase-3 cleavage, and annexin-V signal revealed that apoptosis occurred. Furthermore, when cells entered the mitotic stage, the cell apoptosis was induced by Sp1 overexpression through affecting mitotic chromatin packaging. We also verified that p53 protein was accumulated and activated the p53-dependent apoptotic pathways in the wild-type p53 cells but not in the p53-mutated or p53-deleted cell lines when these cells were infected with adeno-GFP-Sp1 virus. In addition, A549 (p53(+/+)) cells could be protected from apoptosis under Sp1 overexpression when p53 was knockdown by p53 shRNA. Finally, H1299 (p53(-/-)) cell viability was significantly inhibited by adeno-GFP-Sp1 virus infection in the expression of p53. In conclusion, p53 was an essential factor for Sp1 overexpression-induced apoptotic cell death in transforming cells.
Chuang
Jian-Ying
JY
Institute of Basic Medical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
Wu
Chien-Hsing
CH
Lai
Ming-Derg
MD
Chang
Wen-Chang
WC
Hung
Jan-Jong
JJ
D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D002843:Chromatin / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D016329:Sp1 Transcription Factor / Q000502:physiology*; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C493956:CDKN1A protein, human; D002843:Chromatin; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016329:Sp1 Transcription Factor; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53