Article: Monochromosome transfer and microarray analysis identify a critical tumor-suppressive region mapping to chromosome 13q14 and THSD1 in esophageal carcinoma

File Download Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
TitleMonochromosome transfer and microarray analysis identify a critical tumor-suppressive region mapping to chromosome 13q14 and THSD1 in esophageal carcinoma
AuthorsKo, JMY5
Pui, LC5
Wing, LY5
Ho, KC5
King, CC5
Zhuo, YY5
Fung, MK5
Miller, LD2
Liu, ET2
Li, CY5
Lo, PHY5
Stanbridge, EJ4
Tang, JCO1 3
Srivastava, G1
Sai, WT1
Law, S1
Lung, ML5
Issue Date2008
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://mcr.aacrjournals.org/
CitationMolecular Cancer Research, 2008, v. 6 n. 4, p. 592-603 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1541-7786.MCR-07-0154
AbstractLoss of chromosome 13q regions in esophageal squamous cell carcinoma (ESCC) is a frequent event. Monochromosome transfer approaches provide direct functional evidence for tumor suppression by chromosome 13 in SLMT-1, an ESCC cell line, and identify critical regions at 13q12.3, 13q14.11, and 13q14.3. Differential gene expression profiles of three tumor-suppressing microcell hybrids (MCH) and their tumorigenic parental SLMT-1 cell line were revealed by competitive hybridization using 19k cDNA oligonucleotide microarrays. Nine candidate 13q14 tumor-suppressor genes (TSG), including RB1, showed down-regulation in SLMT-1, compared with NE1, an immortalized normal esophageal epithelial cell line; their average gene expression was restored in MCHs compared with SLMT-1. Reverse transcription-PCR validated gene expression levels in MCHs and a panel of ESCC cell lines. Results suggest that the tumor-suppressing effect is not attributed to RB1, but instead likely involves thrombospondin type I domain-containing 1 (THSD1), a novel candidate TSG mapping to 13q14. Quantitative reverse transcription-PCR detected down-regulation of THSD1 expression in 100% of ESCC and other cancer cell lines. Mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation, as analyzed by methylation-specific PCR and clonal bisulfite sequencing. Transfection of wild-type THSD1 into SLMT-1 resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth-suppressive activity. These findings suggest that THSD1 is a good candidate TSG. Copyright © 2008 American Association for Cancer Research.
ISSN1541-7786
2011 Impact Factor: 4.288
2011 SCImago Journal Rankings: 0.680
DOIhttp://dx.doi.org/10.1158/1541-7786.MCR-07-0154
ISI Accession Number IDWOS:000254905600009
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorKo, JMY
dc.contributor.authorPui, LC
dc.contributor.authorWing, LY
dc.contributor.authorHo, KC
dc.contributor.authorKing, CC
dc.contributor.authorZhuo, YY
dc.contributor.authorFung, MK
dc.contributor.authorMiller, LD
dc.contributor.authorLiu, ET
dc.contributor.authorLi, CY
dc.contributor.authorLo, PHY
dc.contributor.authorStanbridge, EJ
dc.contributor.authorTang, JCO
dc.contributor.authorSrivastava, G
dc.contributor.authorSai, WT
dc.contributor.authorLaw, S
dc.contributor.authorLung, ML
dc.date.accessioned2010-09-06T05:58:08Z
dc.date.available2010-09-06T05:58:08Z
dc.date.issued2008
dc.description.abstractLoss of chromosome 13q regions in esophageal squamous cell carcinoma (ESCC) is a frequent event. Monochromosome transfer approaches provide direct functional evidence for tumor suppression by chromosome 13 in SLMT-1, an ESCC cell line, and identify critical regions at 13q12.3, 13q14.11, and 13q14.3. Differential gene expression profiles of three tumor-suppressing microcell hybrids (MCH) and their tumorigenic parental SLMT-1 cell line were revealed by competitive hybridization using 19k cDNA oligonucleotide microarrays. Nine candidate 13q14 tumor-suppressor genes (TSG), including RB1, showed down-regulation in SLMT-1, compared with NE1, an immortalized normal esophageal epithelial cell line; their average gene expression was restored in MCHs compared with SLMT-1. Reverse transcription-PCR validated gene expression levels in MCHs and a panel of ESCC cell lines. Results suggest that the tumor-suppressing effect is not attributed to RB1, but instead likely involves thrombospondin type I domain-containing 1 (THSD1), a novel candidate TSG mapping to 13q14. Quantitative reverse transcription-PCR detected down-regulation of THSD1 expression in 100% of ESCC and other cancer cell lines. Mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation, as analyzed by methylation-specific PCR and clonal bisulfite sequencing. Transfection of wild-type THSD1 into SLMT-1 resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth-suppressive activity. These findings suggest that THSD1 is a good candidate TSG. Copyright © 2008 American Association for Cancer Research.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationMolecular Cancer Research, 2008, v. 6 n. 4, p. 592-603 [How to Cite?]
DOI: http://dx.doi.org/10.1158/1541-7786.MCR-07-0154
dc.identifier.doihttp://dx.doi.org/10.1158/1541-7786.MCR-07-0154
dc.identifier.epage603
dc.identifier.hkuros141625
dc.identifier.isiWOS:000254905600009
dc.identifier.issn1541-7786
2011 Impact Factor: 4.288
2011 SCImago Journal Rankings: 0.680
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmid18403638
dc.identifier.scopuseid_2-s2.0-42049120045
dc.identifier.spage592
dc.identifier.urihttp://hdl.handle.net/10722/67774
dc.identifier.volume6
dc.languageeng
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://mcr.aacrjournals.org/
dc.publisher.placeUnited States
dc.relation.ispartofMolecular Cancer Research
dc.relation.referencesReferences in Scopus
dc.subject.meshAlleles
dc.subject.meshCell Line, Transformed
dc.subject.meshCell Line, Tumor
dc.subject.meshChromosome Mapping
dc.subject.meshChromosome Segregation
dc.subject.meshChromosomes, Human, Pair 13 - genetics
dc.subject.meshDNA Methylation - drug effects
dc.subject.meshDeoxycytidine - pharmacology
dc.subject.meshEpithelial Cells - drug effects - pathology
dc.subject.meshEsophageal Neoplasms - genetics
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation, Neoplastic - drug effects
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshGenome, Human - genetics
dc.subject.meshHumans
dc.subject.meshHydroxamic Acids - pharmacology
dc.subject.meshIn Situ Hybridization, Fluorescence
dc.subject.meshMicroarray Analysis
dc.subject.meshMicrosatellite Repeats - genetics
dc.subject.meshPromoter Regions, Genetic - genetics
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshThrombospondins - genetics - metabolism
dc.subject.meshTransfection
dc.subject.meshTumor Stem Cell Assay
dc.titleMonochromosome transfer and microarray analysis identify a critical tumor-suppressive region mapping to chromosome 13q14 and THSD1 in esophageal carcinoma
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Genome Institute of Singapore
  3. Hong Kong Polytechnic University
  4. UC Irvine
  5. Hong Kong University of Science and Technology