Krüppel-like factor 4 represses transcription of the survivin gene in esophageal cancer cell lines.
Aberrant expression of survivin has been shown to be regulated at the transcription level in cancer cells. In this study, we demonstrate that there are six putative binding sites of Krüppel-like factor 4 (KLF4) within the 2000-bp region upstream of the transcription start site of the human survivin gene. Luciferase reporter gene assays revealed that survivin promoter activity is repressed upon overexpression of KLF4 in EC9706 cells. A chromatin immunoprecipitation assay indicated that KLF4 indeed binds the survivin promoter in vivo. It specifically binds the site located at position -40 among the six binding sites as determined by electrophoretic mobility shift assay. Ectopic expression of KLF4 decreases the mRNA and protein levels of survivin. Furthermore, overexpression of survivin partially reverses KLF4-induced cell apoptosis. These results indicate that KLF4 is a transcriptional repressor of the human survivin gene in esophageal squamous cancer cells.
Laboratory of Cell and Molecular Biology, National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing 100021, PR China.
Guo
G
Zhang
Hongxia
H
Zhu
Yihua
Y
Wang
Shangbin
S
Yang
Mei
M
Liu
Wei
W
Zhang
Lanping
L
Quan
Jinfeng
J
Bai
Zhihua
Z
Liu
Ningzhi
N
Xu
D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism; D004947:Esophagus / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D008869:Microtubule-Associated Proteins; D000077022:Survivin