THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma.
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.
Lung
Hong Lok
HL
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China.
Bangarusamy
Dhinoth Kumar
DK
Xie
Dan
D
Cheung
Arthur Kwok Leung
AK
Cheng
Yue
Y
Kumaran
Mande Kuppusamy
MK
Miller
Lance
L
Liu
Edison Tak-Bun
ET
Guan
Xin-Yuan
XY
Sham
Jonathan Shuntong
JS
Fang
Yan
Y
Li
Liqiong
L
Wang
Nancy
N
Protopopov
Alexey I
AI
Zabarovsky
Eugene R
ER
Tsao
Sai Wah
SW
Stanbridge
Eric J
EJ
Lung
Maria Li
ML
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics; D046228:Microarray Analysis; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D018800:Thy-1 Antigens