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

doi:10.1038/sj.onc.1208812

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 journal › Article › peer-review

115 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 language	English (US)
Pages (from-to)	6525-6532
Number of pages	8
Journal	Oncogene
Volume	24
Issue number	43
DOIs	https://doi.org/10.1038/sj.onc.1208812
State	Published - Sep 29 2005
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.onc.1208812

Cite this

Hong, L. L., Bangarusamy, D. K., Xie, D., Cheung, A. K. L., Cheng, Y., Kumaran, M. K., Miller, L., Liu, E. T. B., Guan, X. Y., Sham, J. S., Fang, Y., Li, L., Wang, N., Protopopov, A. I., Zabarovsky, E. R., Sai, W. T., Stanbridge, E. J., & Lung, M. L. (2005). THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma. Oncogene, 24(43), 6525-6532. https://doi.org/10.1038/sj.onc.1208812

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title = "THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma",

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.",

keywords = "Chromosome 11, Microcell hybrid, Nasopharyngeal carcinoma, Oligo-microarray, THY1",

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

note = "Funding Information: We acknowledge the financial support from the Research Grants Council of the Hong Kong Special Administrative Region, People{\textquoteright}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.",

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month = sep,

day = "29",

doi = "10.1038/sj.onc.1208812",

language = "English (US)",

volume = "24",

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Hong, LL, Bangarusamy, DK, Xie, D, Cheung, AKL, Cheng, Y, Kumaran, MK, Miller, L, Liu, ETB, Guan, XY, Sham, JS, Fang, Y, Li, L, Wang, N, Protopopov, AI, Zabarovsky, ER, Sai, WT, Stanbridge, EJ & Lung, ML 2005, 'THY1 is a candidate tumour suppressor gene with decreased expression in metastatic nasopharyngeal carcinoma', Oncogene, vol. 24, no. 43, pp. 6525-6532. https://doi.org/10.1038/sj.onc.1208812

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

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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