TY - JOUR
T1 - THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma
AU - Hong, Lok Lung
AU - Bangarusamy, Dhinoth Kumar
AU - Xie, Dan
AU - Cheung, Arthur Kwok Leung
AU - Cheng, Yue
AU - Kumaran, Mande Kuppusamy
AU - Miller, Lance
AU - Liu, Edison Tak Bun
AU - Guan, Xin Yuan
AU - Sham, Jonathan Shuntong
AU - Fang, Yan
AU - Li, Liqiong
AU - Wang, Nancy
AU - Protopopov, Alexey I.
AU - Zabarovsky, Eugene R.
AU - Sai, Wah Tsao
AU - Stanbridge, Eric J.
AU - Lung, Maria Li
N1 - 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.
PY - 2005/9/29
Y1 - 2005/9/29
N2 - 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.
AB - 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.
KW - Chromosome 11
KW - Microcell hybrid
KW - Nasopharyngeal carcinoma
KW - Oligo-microarray
KW - THY1
UR - http://www.scopus.com/inward/record.url?scp=26944465443&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208812
DO - 10.1038/sj.onc.1208812
M3 - Article
C2 - 16007174
AN - SCOPUS:26944465443
SN - 0950-9232
VL - 24
SP - 6525
EP - 6532
JO - Oncogene
JF - Oncogene
IS - 43
ER -
