Transcriptional coactivator CBP upregulates hTERT expression and tumor growth and predicts poor prognosis in human lung cancers

• DOI: 10.18632/oncotarget.2430
• Publication Date: 2015-09-15T23:37:56Z
• Authors: Wei Guo; Jianjun Lu; Meng Dai; Taihua Wu; Zhenlong Yu; Jingshu Wang; Wangbing Chen; Dingbo Shi; Wendan Yu; Yao Xiao; Canhui Yi; Zhipeng Tang; Tingting Xu; Xiangsheng Xiao; Yuhui Yuan; Quentin Liu; Guangwei Du; Wuguo Deng
• Keywords: Chromatin immunoprecipitation; Merkel cell polyomavirus

// Wei Guo 1,* , Jianjun Lu 3,* Meng Dai 1 Taihua Wu Zhenlong Yu Jingshu Wang 2 Wangbing Chen Dingbo Shi Wendan Yao Xiao Canhui Yi Zhipeng Tang Tingting Xu Xiangsheng Yuhui Yuan Quentin Liu 1,2 Guangwei Du 4 and Wuguo Deng Institute of Cancer Stem Cell & First Affiliated Hospital, Dalian Medical University, Dalian, China Sun Yat-sen University Cancer Center, State Key Laboratory Oncology in South China; Colaborative Innovation Center Medicine, Guangzhou, 3 Department Thoracic Surgery, The Sun Yat-sen University, Guangzhou, Integrative Biology Pharmacology, University Texas Health Science Center, Houston, Texas, USA * These authors contributed equally to this work Correspondence: Deng, email: Guo, Keywords : CBP, hTERT, promoter, Sp1, lung cancer Received July 17, 2014 Accepted September 02, Published 03, Abstract Upregulated expression activation human telomerase reverse transcriptase (hTERT) is a hallmarker tumorigenesis. However, the mechanism underlying aberrant hTERT activity cells remains poorly understood. In study, we found transcriptional co-activator CBP as new promoter-binding protein that regulated tumor growth adenocarcinoma using biotin-streptavidin-bead pulldown technique. Chromatin immunoprecipitation assay verified immortalized cell cell-specific binding on promoter. Overexpression exogenous upregulated promoter-driven luciferase endogenous cells. Conversely, inhibition by CBP-specific siRNA or its chemical inhibitor repressed well activity. Moreover, also significantly reduced proliferation vitro an xenograft mouse model vivo . Immunohistochemical analysis tissue microarrays cancers revealed positive correlation between hTERT. Importantly, patients with high had shorter overall survival. Furthermore, was interact acetylate transactivator Sp1 Inhibition inhibited acetylation Collectively, our results indicate contributes upregulation growth, overexpression predicts poor prognosis cancers.