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p53 regulates Ki-67 promoter activity through p53- and Sp1-dependent manner in HeLa cells

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Tumor Biology

Abstract

The expression of the human Ki-67 protein, which is strictly associated with cell proliferation, is regulated by a variety of cellular mediators. In this study, we studied the effects of p53 on Ki-67 promoter in HeLa cells using luciferase reporter assay. The results showed that: (1) p53 inhibited Ki-67 promoter activity in a dose-dependent manner, (2) the p53-binding motifs mediated part of the transcriptional repression of Ki-67 promoter through a sequence-specific interaction with p53, (3) p53 was able to repress the Sp1-stimulated Ki-67 promoter activity, and (4) the Sp1-binding sites were responsible for the p53-mediated transcriptional repression of Ki-67 promoter. In conclusion, p53 inhibited Ki-67 promoter activity via p53- and Sp1-dependent pathways, and the interaction between p53 and Sp1 might be involved in the transcriptional regulatory mechanisms.

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Acknowledgments

This project is supported by grants from the National Natural Science Foundation of China (no. 30972976, 81071854), the Science and Technology Department of Jiangsu province (no. BK2009091, BK2010177), and the Program for New Century Excellent Talents in University (NCET-08-0700). We thank Dr. Zhang YP for providing the p53 expression plasmid and Dr. Guntram Suske for Sp1 expression plasmid.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Mei-Juan Wang, Dong-Sheng Pei, Guo-Wei Qian, Qian Cheng, Lian-Tao Li, Hui-Zhong Li & Jun-Nian Zheng

  2. Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China

    Jun-Nian Zheng

  3. School of Pharmacy, Xuzhou Medical College, Xuzhou, 221002, China

    Xiao-Xing Yin

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  1. Mei-Juan Wang
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  2. Dong-Sheng Pei
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Correspondence to Jun-Nian Zheng.

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Mei-Juan Wang and Dong-Sheng Pei contributed equally to this work.

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Wang, MJ., Pei, DS., Qian, GW. et al. p53 regulates Ki-67 promoter activity through p53- and Sp1-dependent manner in HeLa cells. Tumor Biol. 32, 905–912 (2011). https://doi.org/10.1007/s13277-011-0191-4

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  • DOI: https://doi.org/10.1007/s13277-011-0191-4

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