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  • Oncogenomics
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Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9

Oncogene volume 26, pages 148–157 (2007)Cite this article

Abstract

A gene critical to esophageal cancer has been identified. Functional studies using microcell-mediated chromosome transfer of intact and truncated donor chromosomes 3 into an esophageal cancer cell line and nude mouse tumorigenicity assays were used to identify a 1.61 Mb tumor suppressive critical region (CR) mapping to chromosome 3p14.2. This CR is bounded by D3S1600 and D3S1285 microsatellite markers. One candidate tumor suppressor gene, ADAMTS9, maps to this CR. Further studies showed normal expression levels of this gene in tumor-suppressed microcell hybrids, levels that were much higher than observed in the recipient cells. Complete loss or downregulation of ADAMTS9 gene expression was found in 15 out of 16 esophageal carcinoma cell lines. Promoter hypermethylation was detected in the cell lines that do not express this gene. Re-expression of ADAMTS9 was observed after demethylation drug treatment, confirming that hypermethylation is involved in gene downregulation. Downregulation of ADAMTS9 was also found in 43.5 and 47.6% of primary esophageal tumor tissues from Hong Kong and from the high-risk region of Henan, respectively. Thus, this study identifies and provides functional evidence for a CR associated with tumor suppression on 3p14.2 and provides the first evidence that ADAMTS9, mapping to this region, may contribute to esophageal cancer development.

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Acknowledgements

We acknowledge the financial support of the Research Grants Council of the Hong Kong Special Administration Region, China to MLL (HKUST6106/00M).

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Author notes

  1. L C Yang

    Present address: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China

Authors and Affiliations

  1. Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Hong Kong, China

    P H Y Lo, A C C Leung, C Y C Kwok, W S Y Cheung, J M Y Ko, L C Yang & M L Lung

  2. Department of Surgery, University of Hong Kong, Hong Kong, China

    S Law

  3. Henan Key Laboratory for Esophageal Cancer, Laboratory for Cancer Research, Experimental Center for Medicine, Zhengzhou University, Zhengzhou, Henan, China

    L D Wang

  4. Department of Pathology, Yaocun Esophageal Cancer Hospital, Linzhou, Henan, China

    J Li

  5. Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, CA, USA

    E J Stanbridge

  6. Department of Pathology, University of Hong Kong, Hong Kong, China

    G Srivastava & J C O Tang

  7. Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China

    J C O Tang

  8. Department of Anatomy, University of Hong Kong, Hong Kong, China

    S W Tsao

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  1. P H Y Lo
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Correspondence to M L Lung.

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Lo, P., Leung, A., Kwok, C. et al. Identification of a tumor suppressive critical region mapping to 3p14.2 in esophageal squamous cell carcinoma and studies of a candidate tumor suppressor gene, ADAMTS9. Oncogene 26, 148–157 (2007). https://doi.org/10.1038/sj.onc.1209767

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