Abstract
Abstract Human telomerase reverse transcriptase (hTERT) is linked to tumorigenesis and development. However, how hTERT is upregulated in tumor cells remains poorly understood. In this study, we identified CBP as a transcriptional coactivator that specifically binds to hTERT promoter through co-anchoring with transcriptional factors Sp1 and AP-2β and promotes hTERT expression in human lung cancer cells. Streptavidin-agarose pulldown and chromatin immunoprecipitation assays revealed the tumor-specific binding of CBP, Sp1 and AP-2β on the hTERT promoter. The colocalization and interaction between CBP and Sp1 or AP-2β in lung cancer cells were detected. High expression levels of CBP and hTERT in lung cancer cells and tissues were also detected compared to normal lung cells and adjacent normal lung tissues. Tissue array immunohistochemistry of lung adenocarcinomas showed a strong postive correlation between CBP and hTERT expression, and demonstrated the patients with high CBP and hTERT expression had a significantly shorter overall survival than those with low CBP and hTERT expression. Ectopic expression of CBP activated hTERT promoter-driven luciferase gene and endogenous hTERT gene expression in lung cancer cells. Inhibition of CBP expression by CBP-specific siRNA or chemical inhibitor attenuated hTERT promoter-driven luciferase expression and the endogenous hTERT activity, and abrogated the binding of Sp1 and AP-2β on hTERT promoter region. Moreover, CBP knockdown by siRNA significantly inhibited lung cancer cell proliferation, whereas CBP overexpression promoted cell proliferation. These results therefore indicate overexpression of CBP contributes to hTERT upregulation through its cooperation with transactivators Sp1 and AP-2β and predicts poor prognosis in human lung cancers. Note: This abstract was not presented at the meeting. Citation Format: Wei Guo. Transcriptional coactivator CBP regulates hTERT expression through the cooperation with Sp1/AP-2β and predicts poor prognosis in human lung cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 471. doi:10.1158/1538-7445.AM2014-471
Published Version
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