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

• Published in: Oncogene Vol. 24; no. 43; pp. 6525 - 6532
• Main Authors: HONG LOK LUNG, DHINOTH KUMAR BANGARUSAMY, YAN FANG, LIQIONG LI, WANG, Nancy, PROTOPOPOV, Alexey I, ZABAROVSKY, Eugene R, SAI WAH TSAO, STANBRIDGE, Eric J, MARIA LI LUNG, DAN XIE, ARTHUR KWOK LEUNG CHEUNG, YUE CHENG, MANDE KUPPUSAMY KUMARAN, MILLER, Lance, LIU, Edison Tak-Bun, GUAN, Xin-Yuan, JONATHAN SHUNTONG SHAM
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 29.09.2005; Nature Publishing Group
• Subjects: Biological and medical sciences; Carcinoma - genetics; Carcinoma - pathology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosomes; Chromosomes, Human, Pair 11; DNA Methylation; DNA microarrays; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation, Neoplastic; Gene Silencing; Genes, Tumor Suppressor; Genomics; Humans; Hybrids; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis - genetics; Lymphatic system; Medical sciences; Medicin och hälsovetenskap; Metastases; Metastasis; Microarray Analysis; Molecular and cellular biology; Nasopharyngeal carcinoma; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Oligonucleotides; Otorhinolaryngology. Stomatology; Ovarian cancer; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; Throat cancer; Thy-1 Antigens - genetics; Thy-1 Antigens - metabolism; Transfection; Tumor Cells, Cultured; Tumor Stem Cell Assay; Tumor suppressor genes; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Hong Kong China; China; Singapore; nasopharyngeal carcinoma; Hybrid; Malignant tumor; Nasopharynx carcinoma; Metastasis; THY1; microcell hybrid; Gene expression; Microarray; Carcinogenesis; oligo-microarray; Chromosome 11; ENT disease; Pharynx disease; Candidate gene; Tumor suppressor gene
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1208812

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.