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

Lung Yau Wing, Lok Lung Hong, Eugene R. Zabarovsky, Michael I. Lerman, Jonathan Shun Tong Sham, Daniel Tsin Tien Chua, Sai Wah Tsao, Eric J. Stanbridge, Maria Li Lung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2821-2826
Number of pages6
JournalInternational Journal of Cancer
Volume119
Issue number12
DOIs
Publication statusPublished - 15 Dec 2006

Scopus Subject Areas

  • Oncology
  • Cancer Research

User-Defined Keywords

  • BLU/ZMYND10
  • Chromosome 3p21.3
  • Nasopharyngeal carcinoma
  • Tumor suppressor gene

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