Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma.
Overexpression of human pituitary tumor transforming gene (PTTG) is wildly detected in many tumors, including esophageal cancer. Besides overexpression of PTTG in esophageal squamous cell carcinoma (ESCC) tissues and cells, we detected accumulation of cytoplasmic beta-catenin in ESCC. In our study, a putative TCF4-binding element (TBE) was identified in PTTG promoter region. The activity of PTTG promoter containing the TBE was activated by S37Abeta-catenin and inhibited by dominant-negative TCF. Furthermore, the activation by S37Abeta-catenin was mostly abrogated among PTTG promoter region without the TBE or with a mutant one. By using biotin-streptavidin pull-down assay, we also found that the TBE among PTTG promoter bound to TCF-4 protein. Moreover, levels of PTTG mRNA and protein were increased by S37Abeta-catenin. Finally, it is noticeable that we detected a correlation between beta-catenin localization and PTTG expression in 69 primary ESCC (p<0.01). In brief, our study shows that overexpression of PTTG in ESCC is likely due to the activation of beta-catenin/WNT signaling. As a target gene of beta-catenin/TCF pathway, PTTG may play an important role in tumorigenesis of human ESCC.
Zhou
Cuiqi
C
Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Liu
Shuang
S
Zhou
Xiaobo
X
Xue
Liyan
L
Quan
Lanping
L
Lu
Ning
N
Zhang
Guo
G
Bai
Jinfeng
J
Wang
Yihua
Y
Liu
Zhihua
Z
Zhan
Qimin
Q
Zhu
Hongxia
H
Xu
Ningzhi
N
D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D004938:Esophageal Neoplasms / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D064249:Securin; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000502:physiology*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D064249:Securin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; C578002:pituitary tumor-transforming protein 1, human