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Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer

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Tumor Biology

Abstract

The potential anti-senescence gene Klotho (KL) has been recently found to participate in the progression of several different human cancers including breast, lung, and cervical cancer. In this current study, we identified KL as a candidate tumor suppressor gene silenced through promoter hypermethylation in colorectal cancer (CRC). KL gene expression is found to be absent or reduced in colon cancer cell lines (5/6, 83.3%), which can be reversed by treatment with demethylation agent 5-aza-2′-deoxycytidine (Aza), but not HDAC inhibitor trichostatin A. In addition, KL expression is markedly downregulated in colorectal carcinoma tissues when compared to the adjacent nontumor tissues (n = 25, p < 0.001). The methylation of the KL gene promoter was frequently detected in primary tumor tissues (34/40, 85%) when compared with adjacent nontumor colon tissues. Furthermore, ectopic expression of KL led to the cell proliferation inhibition of colon cancer cell lines via the induction of cell apoptosis and S-phase cell cycle arrest. Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC.

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Acknowledgments

The study was supported by the National Natural Scientific Foundation of China (30900676,81071963). We thank Dr. Manish Gala and Prof/Dr. Georg Enders for critical review and editing of the manuscript.

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Authors and Affiliations

  1. Department of Gastroenterology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Jie Pan, Jing Zhong, Li Hong Gan & Liang Jing Wang

  2. Laboratory of Digestive Disease, Clinical Institution of Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China

    Jie Pan & Shu Jie Chen

  3. Key Laboratory of Biotherapy of Zhejiang Province, Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine Zhejiang University, Hangzhou, China

    Hong Chuan Jin & Xian Wang

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  1. Jie Pan
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  2. Jing Zhong
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  5. Hong Chuan Jin
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  7. Liang Jing Wang
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Correspondence to Xian Wang or Liang Jing Wang.

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Jie Pan and Jing Zhong contributed equally to this work.

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Pan, J., Zhong, J., Gan, L.H. et al. Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer. Tumor Biol. 32, 729–735 (2011). https://doi.org/10.1007/s13277-011-0174-5

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  • DOI: https://doi.org/10.1007/s13277-011-0174-5

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