Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma

Lok Lung Hong, Cathy Carfield Lo, Carmen Chak Lui Wong, Arthur Kwok Leung Cheung, Fu Cheong Ka, Nathalie Wong, Mei Kwong Fung, Chi Chan King, Evan Wai Lok Law, Wah Tsao Sai, Daniel Chua, Jonathan Shuntong Sham, Yue Cheng, Eric J. Stanbridge, Gavin Robertson, Maria Li Lung

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Abstract

In previous studies, we successfully refined nasopharyngeal carcinoma (NPC) critical regions (CRs) mapping to chromosome 11q13 and 11q22-23. The chromosome 11 fragment containing the 1.8 Mb NPC CR at 11q13 (CR1), the CR at 11q22.3 mapped near D11S2000 (CR2), part of the CR at 11q23.1-11q23.2 overlapping with D11S1300 and D11S1391 (CR3), and the CR at cell adhesion molecule 1 (CADM1) locus (CR4), was chosen as the chromosome 11 donor cell line for the present study. Gamma irradiation was applied to cleave this truncated chromosome into smaller fragments and a new panel of donor cells containing further deleted fragments was produced. Subclones XMCH3.2 and XMCH3.4 were chosen for subsequent transfer to HONE1 cells; each contains a single copy of deleted chromosome 11 fragment with or without CR2 and the THY1 locus, previously shown to be involved in NPC. Both resultant chromosome 11 fragments in XMCH3.2 and XMCH3.4 caused tumor suppression. The association of alpha B-crystallin (CRYAB), a gene identified as being differentially expressed by gene profiling of NPC and an immortalized nasopharyngeal epithelial cell line, and which is located near CR3, was found to be associated with tumor suppression in all the tumor-suppressive hybrids. In addition, the expression level of this gene was down-regulated in the 7 NPC cell lines and in 5 out of 14 normal/tumor tissue pairs in the present study. Both promoter hypermethylation and allelic loss may be involved in the inactivation of this gene, suggesting its possible role in NPC development.

Original languageEnglish (US)
Pages (from-to)1288-1296
Number of pages9
JournalInternational Journal of Cancer
Volume122
Issue number6
DOIs
StatePublished - Mar 15 2008

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alpha-Crystallin B Chain
Chromosomes, Human, Pair 11
Chromosomes
Neoplasms
Cell Line
Loss of Heterozygosity
Chromosome Mapping
Cell Adhesion Molecules
Gene Silencing
Genes
Nasopharyngeal carcinoma
Epithelial Cells
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hong, Lok Lung ; Lo, Cathy Carfield ; Wong, Carmen Chak Lui ; Cheung, Arthur Kwok Leung ; Ka, Fu Cheong ; Wong, Nathalie ; Fung, Mei Kwong ; King, Chi Chan ; Law, Evan Wai Lok ; Sai, Wah Tsao ; Chua, Daniel ; Sham, Jonathan Shuntong ; Cheng, Yue ; Stanbridge, Eric J. ; Robertson, Gavin ; Lung, Maria Li. / Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma. In: International Journal of Cancer. 2008 ; Vol. 122, No. 6. pp. 1288-1296.
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title = "Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma",
abstract = "In previous studies, we successfully refined nasopharyngeal carcinoma (NPC) critical regions (CRs) mapping to chromosome 11q13 and 11q22-23. The chromosome 11 fragment containing the 1.8 Mb NPC CR at 11q13 (CR1), the CR at 11q22.3 mapped near D11S2000 (CR2), part of the CR at 11q23.1-11q23.2 overlapping with D11S1300 and D11S1391 (CR3), and the CR at cell adhesion molecule 1 (CADM1) locus (CR4), was chosen as the chromosome 11 donor cell line for the present study. Gamma irradiation was applied to cleave this truncated chromosome into smaller fragments and a new panel of donor cells containing further deleted fragments was produced. Subclones XMCH3.2 and XMCH3.4 were chosen for subsequent transfer to HONE1 cells; each contains a single copy of deleted chromosome 11 fragment with or without CR2 and the THY1 locus, previously shown to be involved in NPC. Both resultant chromosome 11 fragments in XMCH3.2 and XMCH3.4 caused tumor suppression. The association of alpha B-crystallin (CRYAB), a gene identified as being differentially expressed by gene profiling of NPC and an immortalized nasopharyngeal epithelial cell line, and which is located near CR3, was found to be associated with tumor suppression in all the tumor-suppressive hybrids. In addition, the expression level of this gene was down-regulated in the 7 NPC cell lines and in 5 out of 14 normal/tumor tissue pairs in the present study. Both promoter hypermethylation and allelic loss may be involved in the inactivation of this gene, suggesting its possible role in NPC development.",
author = "Hong, {Lok Lung} and Lo, {Cathy Carfield} and Wong, {Carmen Chak Lui} and Cheung, {Arthur Kwok Leung} and Ka, {Fu Cheong} and Nathalie Wong and Fung, {Mei Kwong} and King, {Chi Chan} and Law, {Evan Wai Lok} and Sai, {Wah Tsao} and Daniel Chua and Sham, {Jonathan Shuntong} and Yue Cheng and Stanbridge, {Eric J.} and Gavin Robertson and Lung, {Maria Li}",
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Hong, LL, Lo, CC, Wong, CCL, Cheung, AKL, Ka, FC, Wong, N, Fung, MK, King, CC, Law, EWL, Sai, WT, Chua, D, Sham, JS, Cheng, Y, Stanbridge, EJ, Robertson, G & Lung, ML 2008, 'Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma', International Journal of Cancer, vol. 122, no. 6, pp. 1288-1296. https://doi.org/10.1002/ijc.23259

Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma. / Hong, Lok Lung; Lo, Cathy Carfield; Wong, Carmen Chak Lui; Cheung, Arthur Kwok Leung; Ka, Fu Cheong; Wong, Nathalie; Fung, Mei Kwong; King, Chi Chan; Law, Evan Wai Lok; Sai, Wah Tsao; Chua, Daniel; Sham, Jonathan Shuntong; Cheng, Yue; Stanbridge, Eric J.; Robertson, Gavin; Lung, Maria Li.

In: International Journal of Cancer, Vol. 122, No. 6, 15.03.2008, p. 1288-1296.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of tumor suppressive activity by irradiation microcell-mediated chromosome transfer and involvement of alpha B-crystallin in nasopharyngeal carcinoma

AU - Hong, Lok Lung

AU - Lo, Cathy Carfield

AU - Wong, Carmen Chak Lui

AU - Cheung, Arthur Kwok Leung

AU - Ka, Fu Cheong

AU - Wong, Nathalie

AU - Fung, Mei Kwong

AU - King, Chi Chan

AU - Law, Evan Wai Lok

AU - Sai, Wah Tsao

AU - Chua, Daniel

AU - Sham, Jonathan Shuntong

AU - Cheng, Yue

AU - Stanbridge, Eric J.

AU - Robertson, Gavin

AU - Lung, Maria Li

PY - 2008/3/15

Y1 - 2008/3/15

N2 - In previous studies, we successfully refined nasopharyngeal carcinoma (NPC) critical regions (CRs) mapping to chromosome 11q13 and 11q22-23. The chromosome 11 fragment containing the 1.8 Mb NPC CR at 11q13 (CR1), the CR at 11q22.3 mapped near D11S2000 (CR2), part of the CR at 11q23.1-11q23.2 overlapping with D11S1300 and D11S1391 (CR3), and the CR at cell adhesion molecule 1 (CADM1) locus (CR4), was chosen as the chromosome 11 donor cell line for the present study. Gamma irradiation was applied to cleave this truncated chromosome into smaller fragments and a new panel of donor cells containing further deleted fragments was produced. Subclones XMCH3.2 and XMCH3.4 were chosen for subsequent transfer to HONE1 cells; each contains a single copy of deleted chromosome 11 fragment with or without CR2 and the THY1 locus, previously shown to be involved in NPC. Both resultant chromosome 11 fragments in XMCH3.2 and XMCH3.4 caused tumor suppression. The association of alpha B-crystallin (CRYAB), a gene identified as being differentially expressed by gene profiling of NPC and an immortalized nasopharyngeal epithelial cell line, and which is located near CR3, was found to be associated with tumor suppression in all the tumor-suppressive hybrids. In addition, the expression level of this gene was down-regulated in the 7 NPC cell lines and in 5 out of 14 normal/tumor tissue pairs in the present study. Both promoter hypermethylation and allelic loss may be involved in the inactivation of this gene, suggesting its possible role in NPC development.

AB - In previous studies, we successfully refined nasopharyngeal carcinoma (NPC) critical regions (CRs) mapping to chromosome 11q13 and 11q22-23. The chromosome 11 fragment containing the 1.8 Mb NPC CR at 11q13 (CR1), the CR at 11q22.3 mapped near D11S2000 (CR2), part of the CR at 11q23.1-11q23.2 overlapping with D11S1300 and D11S1391 (CR3), and the CR at cell adhesion molecule 1 (CADM1) locus (CR4), was chosen as the chromosome 11 donor cell line for the present study. Gamma irradiation was applied to cleave this truncated chromosome into smaller fragments and a new panel of donor cells containing further deleted fragments was produced. Subclones XMCH3.2 and XMCH3.4 were chosen for subsequent transfer to HONE1 cells; each contains a single copy of deleted chromosome 11 fragment with or without CR2 and the THY1 locus, previously shown to be involved in NPC. Both resultant chromosome 11 fragments in XMCH3.2 and XMCH3.4 caused tumor suppression. The association of alpha B-crystallin (CRYAB), a gene identified as being differentially expressed by gene profiling of NPC and an immortalized nasopharyngeal epithelial cell line, and which is located near CR3, was found to be associated with tumor suppression in all the tumor-suppressive hybrids. In addition, the expression level of this gene was down-regulated in the 7 NPC cell lines and in 5 out of 14 normal/tumor tissue pairs in the present study. Both promoter hypermethylation and allelic loss may be involved in the inactivation of this gene, suggesting its possible role in NPC development.

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DO - 10.1002/ijc.23259

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