THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma

Lok Lung Hong, Dhinoth Kumar Bangarusamy, Dan Xie, Arthur Kwok Leung Cheung, Yue Cheng, Mande Kuppusamy Kumaran, Lance Miller, Edison Tak Bun Liu, Xin Yuan Guan, Jonathan Shuntong Sham, Yan Fang, Liqiong Li, Nancy Wang, Alexey I. Protopopov, Eugene R. Zabarovsky, Wah Tsao Sai, Eric J. Stanbridge, Maria Li Lung*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

Using oligonucleotide microarray analysis, THY1, mapping close to a previously defined 11q22-23 nasopharyngeal carcinoma (NPC) critical region was identified as showing consistent downregulated expression in the tumour segregants, as compared to their parental tumour-suppressing microcell hybrids (MCHs). Gene expression and protein analyses show that THY1 was not expressed in the NPC HONE1 recipient cells, tumour segregants, and other NPC cell lines; THY1 was exclusively expressed in the non-tumourigenic MCHs. The mechanism of THY1 gene inactivation in these cell lines was attributed to hypermethylation. Clinical study showed that in 65% of NPC specimens there was either downregulation or loss of THY1 gene expression. Using a tissue microarray and immunohistochemical staining, 44% of the NPC cases showed downregulated expression of THY1 and 9% lost THY1 expression. The frequency of THY1 downregulated expression in lymph node metastatic NPC was 63%, which was significantly higher than in the primary tumour (33%). After transfection of THY1 gene into HONE1 cells, a dramatic reduction of colony formation ability was observed. These findings suggest that THY1 is a good candidate tumour suppressor gene in NPC, which is significantly associated with lymph node metastases.

Original languageEnglish (US)
Pages (from-to)6525-6532
Number of pages8
JournalOncogene
Volume24
Issue number43
DOIs
StatePublished - Sep 29 2005
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge the financial support from the Research Grants Council of the Hong Kong Special Administrative Region, People’s Republic of China: Grant numbers HKUST 6113/01M, CA99/00.SC02, and CA03/04.SC01 to MLL, the Agency for Science Technology and Research, Singapore to EL, and the Swedish Cancer Society, the Swedish Research Council, STINT, the Swedish Institute, the Royal Swedish Academy of Sciences and INTAS to ERZ.

Keywords

  • Chromosome 11
  • Microcell hybrid
  • Nasopharyngeal carcinoma
  • Oligo-microarray
  • THY1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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