학술논문
THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma.
Document Type
Article
Author
Hong Lok Lung; Bangarusamy, Dhinoth Kumar; Dan Xie; Kwok Leung Cheung, Arthur; Yue Cheng; Kumaran, Mande Kuppusamy; Miller, Lance; Tak-Bun Liu, Edison; Xin-Yuan Guan; Shuntong Sham, Jonathan; Yan Fang; Liqiong Li; Wang, Nancy; Protopopov, Alexey I.; Zabarovsky, Eugene R.; Sai Wah Tsao; Stanbridge, Eric J.; Li Lung, Maria
Source
Subject
*PHARYNGEAL cancer
*TUMOR suppressor genes
*GENE expression
*PROTEIN analysis
*CELL lines
*CANCER cells
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Language
ISSN
0950-9232
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.Oncogene (2005) 24, 6525–6532. doi:10.1038/sj.onc.1208812; published online 20 June 2005 [ABSTRACT FROM AUTHOR]