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Acta Biochimica et Biophysica Sinica 2009 41(6):504-514; doi:10.1093/abbs/gmp039
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

NGX6 inhibits AP-1 and Ets-1 expression and down-regulates cyclin D1 in human colorectal cancer

Ya Peng1,#, Hongtao Li1,#, Minghua Wu2, Xiaoyan Wang1, Songqing Fan3, Fen Liu1, Bo Xiang2, Qin Guo1, Xueyuan Tang1 and Shourong Shen1,*

1 The Third Affiliated Hospital, Xiangya School of Medicine, Central South University, Changsha 410013, China
2 Cancer Research Institute, Central South University, Changsha 410078, China
3 The Second Affiliated Hospital, Xiang Ya School of Medicine, Central South University, Changsha 410011, China

* Correspondence address. Tel: +86-731-8618457; E-mail: ssr-35403{at}163.com


  Abstract

Colorectal cancer (CRC) is a common malignant tumor that is associated with an increased incidence of morbidity and mortality. Nasopharyngeal carcinoma-associated gene 6 (NGX6) is a novel candidate suppressor gene of tumor metastasis, which is down-regulated in CRC. In the present study, we constructed a colorectal tissue microarray to examine the expression profiles of NGX6, phospho-c-Jun N-terminal kinase (p-JNK), and phospho-extracellular signal-regulated kinase (p-ERK ) in CRC tissues. We found that the NGX6 expression was lower in CRC tissues and metastatic lymph nodes, whereas the expressions of p-JNK and p-ERK were higher in CRC tissues, than in normal intestinal mucosa. The expressions of NGX6, p-JNK, and p-ERK were associated with the clinical pathological features of colorectal tissues. NGX6 overexpression inhibited the activation and nuclear translocation of JNK1, which led to an accumulation of p-JNK in the cytoplasm, but did not inhibit the activation and nuclear translocation of ERK1/2. NGX6 also inhibited the expression of the transcription factors AP-1 (c-jun and c-fos) and Ets-1. In addition, NGX6 overexpression decreased the expression of cyclin D1 and dramatically suppressed the transcriptional efficiency of the cyclin D1 promoter. We propose that NGX6 expression is lost in the multi-step process of human colorectal carcinogenesis. Its overexpression can inhibit the expression of transcription factors AP-1 and Ets-1, and down-regulate the transcriptional activity of the cyclin D1 promoter in human CRC.

Keywords    NGX6; colorectal cancer; tissue microarray; SAPK/JNK pathway; AP-1

Received: December 18, 2008; Accepted: March 10, 2009

# These authors equally contributed to this work.


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