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Aberrant activation of Hedgehog pathway in Nasopharyngeal carcinoma

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Abstract

Nasopharyngeal carcinoma (NPC) is a very common head and neck cancer in southern china. Despite advances in surgical and chemotherapeutic approaches, its prognosis is still not promising. Hedgehog signaling pathway was reported to be involved in a number of cancers including head and neck. However, it remains unclear regarding the role of this pathway in NPC. By real-time PCR, we found Ptch1, Smo, and Gli-1 were expressed in all human nasopharyngeal epithelial tissues and cell lines. Compared with nasopharyngeal normal epithelial tissues, the mRNA expression level of Gli-1 was higher in carcinoma and nasopharyngitis (NPI) epithelial tissues. While compared with nasopharyngitis epithelia, the mRNA expression level of Ptch1 was lower in carcinoma epithelia and normal epithelia. The expressions of Smo mRNA were not significantly different among these epithelial tissues. Immunohistochemistry analysis revealed that the expression level of Gli-1 was higher in NPC than NPI. Thus, our data indicated that aberrant activation of hedgehog pathway in NPC. Furthermore, blocking the pathway with cyclopamine inhibited the proliferation of NPC epithelia cell lines. In addition, blockade of the pathway in three NPC cell lines with cyclopamine-induced tumor cell apoptosis. The transcription of hedgehog target genes also is inhibited by cyclopamine. These data suggested that hedgehog pathway may sustain nasopharyngeal tumor growth. Our data demonstrated that hedgehog signaling pathway was involved in NPC pathogenesis and might be a novel therapeutic target for NPC.

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Acknowledgments

This work was partially supported by the Science and Technology Foundation of Technology-bureau of Guangdong province (2008B030301136, 2010B031500028). We thank the Center Laboratory of Guangzhou First Municipal People’s Hospital, for technical support in our experiment and analysis. Thanks to Guangzhou Institute of Respiratory Disease for real-time PCR and Immunohistochemistry experiment and analysis. Thanks to all of the hospital provide nasopharyngeal epithelia samples. Thanks to Doctor Xiangbin Xing for the help of writing the paper. We are grateful to all the participants that made this study possible.

Conflict of interest

All authors disclose any association that poses a conflict of interest in connection with the manuscript.

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Authors and Affiliations

  1. Life Science College, Sun Yat-sen University, No. 135 Xingang xi Road, Guangzhou, 510275, China

    Yongjian Yue, Baiyu Xiao, Guoping Zhang, Funeng Jiang, Jinglin Zhang, Changhua Chen, Peizhou Yang & Hong Chang

  2. Huangpu Branch, Sun Yat-sen University First Affiliated Hospital, No. 183 Huangpu East Road, Guangzhou, 510700, China

    Genwang Pei & Hua Dang

  3. Department of Urology, Guangzhou First Municipal People’s Hospital, Affiliated Guangzhou Medical College, Guangzhou, China

    Weide Zhong

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  1. Yongjian Yue
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  2. Weide Zhong
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  3. Genwang Pei
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  4. Baiyu Xiao
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  9. Peizhou Yang
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  10. Hua Dang
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  11. Hong Chang
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Correspondence to Hua Dang or Hong Chang.

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The authors Yongjian Yue, Weide Zhong, and Genwang Pei contributed equally to this work.

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Yue, Y., Zhong, W., Pei, G. et al. Aberrant activation of Hedgehog pathway in Nasopharyngeal carcinoma. Clin Exp Med 13, 315–322 (2013). https://doi.org/10.1007/s10238-012-0198-1

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  • DOI: https://doi.org/10.1007/s10238-012-0198-1

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