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Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma

Oncogene volume 28, pages 2821–2828 (2009)Cite this article

Abstract

Deletion of 3p is one of the most frequent genetic alterations in many tumors, including esophageal squamous cell carcinoma (ESCC). In our recent study, deletion of 3p24 was frequently detected in ESCC and one candidate tumor suppressor gene (TSG), p300/CBP-associated factor (PCAF), was identified within the region. In this study, downregulation of PCAF was detected in 23/40 (57.5%) of primary ESCCs and 4/9 (44.4%) of the ESCC cell lines. A further study found that downregulation of PCAF was also associated with hypermethylation of the promoter region of PCAF gene. Methylation-specific PCR found that promoter methylation was detected in 28/40 (70%) of primary ESCCs and 5/9 (55.6%) of ESCC cell lines. In addition, the expression of PCAF could be reactivated in ESCC cell line KYSE510 after demethylation treatment with 5-aza-dC. Functional studies showed that PCAF was able to suppress tumorigenicity of ESCC cells both in vitro and in vivo, including foci formation, colony formation in soft agar and tumor formation in nude mice. Molecular study found that the tumor suppressive mechanism of PCAF was associated with its role in cell cycle arrest at the G1/S checkpoint by the downregulation of CDK2 and upregulation of p21waf1/Cip1, Smad4, Rb and p27Kip1. In conclusion, PCAF might be the target TSG responsible for the 3p24 deletion event, which has an important role in the development and progression of ESCC.

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Acknowledgements

This work was supported by Research Grant Council Central Allocation (HKUST 2/06C), Sun Yat-Sen University ‘Hundred Talents Program’ (85000-3171311), a grant from the Major State Basic Research Program of China (2006CB910104) and a grant from the National Natural Science Foundation of China (30772475).

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Author notes

  1. C Zhu and Y-R Qin: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong, China

    C Zhu, D T T Chua, J M Fung, L Chen, L Fu, L Hu & X-Y Guan

  2. Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China

    Y-R Qin

  3. State Key Laboratory of Oncology in Southern China, and Cancer Center, Sun Yat-Sen University, Guangzhou, China

    D Xie & X-Y Guan

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  1. C Zhu
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Correspondence to X-Y Guan.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Zhu, C., Qin, YR., Xie, D. et al. Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma. Oncogene 28, 2821–2828 (2009). https://doi.org/10.1038/onc.2009.137

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