Volume 119, Issue 12 pp. 2821-2826
Cancer Genetics

Functional studies of the chromosome 3p21.3 candidate tumor suppressor gene BLU/ZMYND10 in nasopharyngeal carcinoma

Wing Lung Yau

Wing Lung Yau

Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Hong Kong (SAR), China

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Hong Lok Lung

Hong Lok Lung

Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Hong Kong (SAR), China

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Eugene R. Zabarovsky

Eugene R. Zabarovsky

Microbiology and Tumor Biology Center and Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden

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Michael I. Lerman

Michael I. Lerman

Laboratory of Immunobiology, Center for Cancer Research, National Cancer Institute, Frederick, MD

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Jonathan Shun-tong Sham

Jonathan Shun-tong Sham

Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), China

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Daniel Tsin-tien Chua

Daniel Tsin-tien Chua

Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong (SAR), China

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Sai Wah Tsao

Sai Wah Tsao

Department of Anatomy, University of Hong Kong, Pokfulam, Hong Kong (SAR), China

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Eric J. Stanbridge

Eric J. Stanbridge

Department of Microbiology and Molecular Genetics, University of California, Irvine, CA

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Maria Li Lung

Corresponding Author

Maria Li Lung

Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Hong Kong (SAR), China

Fax: +852-2358-1559.

Department of Biology and Center for Cancer Research, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong (SAR), ChinaSearch for more papers by this author
First published: 26 October 2006
Citations: 40

This article is a US Government work and, as such, is in the public domain in the United States of America.

Abstract

Chromosome 3p plays an important role in tumorigenesis in many cancers, including nasopharyngeal carcinoma (NPC). We have previously shown chromosome 3p can suppress tumor growth in vivo by using the monochromosome transfer approach, which indicated the chromosome 3p21.3 region was critical for tumor suppression. BLU/ZMYND10 is one of the candidate tumor suppressor genes mapping in the 3p21.3 critical region and is a candidate TSG for NPC. By quantitative RT-PCR, it is frequently downregulated in NPC cell lines (83%) and NPC biopsies (80%). However, no functional studies have yet verified the functional role of BLU/ZMYND10 as a tumor suppressor gene. In the current study, a gene inactivation test (GIT) utilizing a tetracycline regulation system was used to study the functional role of BLU/ZMYND10. When BLU/ZMYND10 is expressed in the absence of doxycycline, the stable transfectants were able to induce tumor suppression in nude mice. In contrast, downregulation of BLU/ZMYND10 in these tumor suppressive clones by doxycycline treatment restored the tumor formation ability. This study provides the first significant evidence to demonstrate BLU/ZMYND10 can functionally suppress tumor formation in vivo and is, therefore, likely to be one of the candidate tumor suppressor genes involved in NPC. Published 2006 Wiley-Liss, Inc.

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