Zhou, Cuiqi, Liu, Shuang, Zhou, Xiaobo, Xue, Liyan, Quan, Lanping, Lu, Ning, Zhang, Guo, Bai, Jinfeng, Wang, Yihua, Liu, Zhihua, Zhan, Qimin, Zhu, Hongxia and Xu, Ningzhi (2005) Overexpression of human pituitary tumor transforming gene (hPTTG), is regulated by beta-catenin /TCF pathway in human esophageal squamous cell carcinoma. International Journal of Cancer, 113 (6), 891-898. (doi:10.1002/ijc.20642). (PMID:15514942)
Abstract
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 ?-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 S37A?-catenin and inhibited by dominant-negative TCF. Furthermore, the activation by S37A?-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 S37A?-catenin. Finally, it is noticeable that we detected a correlation between ?-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 ?-catenin/WNT signaling. As a target gene of ?-catenin/TCF pathway, PTTG may play an important role in tumorigenesis of human ESCC
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