Article: Functional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma

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TitleFunctional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma
AuthorsLeung Cheung, AK7
Lung, HL7
Hung, SC7
Law, EWL7
Cheng, Y5 7
Yau, WL7
Bangarusamy, DK4
Miller, LD4
Liu, ETB4
Shao, JY2
Kou, CW2
Chua, D3
Zabarovsky, ER1
Tsao, SW3
Stanbridge, EJ6
Lung, ML7
KeywordsMolecular Sequence Numbers
Issue Date2008
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
CitationCancer Research, 2008, v. 68 n. 19, p. 8137-8145 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-08-0904
AbstractFunctional studies to identify the potential role of a chromosome 3p14-21 gene, protein tyrosine phosphatase receptor type G (PTPRG), were performed. PTPRG was identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC)by differential gene profiling of tumorigenic and nontumorigenic NPC chromosome 3 microcell hybrids (MCH). Down-regulation of this gene was found in tumor segregants when compared with their corresponding tumor-suppressive MCHs, as well as in NPC cell lines and tumor biopsies. Promoter hypermethylation and loss of heterozygosity were found to be important mechanisms contributing to PTPRG silencing. PTPRG overexpression in NPC cell lines induces growth suppression and reduced anchorage-independent growth in vitro. This is the first study to use a tetracycline-responsive vector expression system to study PTPRG stable transfectants. Results indicate its ability to induce significant tumor growth suppression in nude mice under conditions activating transgene expression. These studies now provide functional evidence indicating critical interactions of PTPRG in the extracellular matrix milieu induce cell arrest and changes in cell cycle status. This is associated with inhibition of pRB phosphorylation through down-regulation of cyclin D1. These novel findings enhance our current understanding of how PTPRG may contribute to tumorigenesis. ©2008 American Association for Cancer Research.
ISSN0008-5472
2011 Impact Factor: 7.856
2011 SCImago Journal Rankings: 1.309
DOIhttp://dx.doi.org/10.1158/0008-5472.CAN-08-0904
ISI Accession Number IDWOS:000260029900053
Funding AgencyGrant Number
People's Republic of ChinaHKUST6112/04M
Swedish Cancer Society
Swedish Research Council
Swedish Institute
Royal Swedish Academy of Sciences
Karohnska Institute
Funding Information:

Grant support: Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China grant HKUST6112/04M (M.L. Lung), and Swedish Cancer Society, Swedish Research Council, Swedish Institute, Royal Swedish Academy of Sciences, and Karohnska Institute (E.R. Zabarovsky).

ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorLeung Cheung, AK
dc.contributor.authorLung, HL
dc.contributor.authorHung, SC
dc.contributor.authorLaw, EWL
dc.contributor.authorCheng, Y
dc.contributor.authorYau, WL
dc.contributor.authorBangarusamy, DK
dc.contributor.authorMiller, LD
dc.contributor.authorLiu, ETB
dc.contributor.authorShao, JY
dc.contributor.authorKou, CW
dc.contributor.authorChua, D
dc.contributor.authorZabarovsky, ER
dc.contributor.authorTsao, SW
dc.contributor.authorStanbridge, EJ
dc.contributor.authorLung, ML
dc.date.accessioned2010-09-17T10:15:47Z
dc.date.available2010-09-17T10:15:47Z
dc.date.issued2008
dc.description.abstractFunctional studies to identify the potential role of a chromosome 3p14-21 gene, protein tyrosine phosphatase receptor type G (PTPRG), were performed. PTPRG was identified as a candidate tumor suppressor gene (TSG) in nasopharyngeal carcinoma (NPC)by differential gene profiling of tumorigenic and nontumorigenic NPC chromosome 3 microcell hybrids (MCH). Down-regulation of this gene was found in tumor segregants when compared with their corresponding tumor-suppressive MCHs, as well as in NPC cell lines and tumor biopsies. Promoter hypermethylation and loss of heterozygosity were found to be important mechanisms contributing to PTPRG silencing. PTPRG overexpression in NPC cell lines induces growth suppression and reduced anchorage-independent growth in vitro. This is the first study to use a tetracycline-responsive vector expression system to study PTPRG stable transfectants. Results indicate its ability to induce significant tumor growth suppression in nude mice under conditions activating transgene expression. These studies now provide functional evidence indicating critical interactions of PTPRG in the extracellular matrix milieu induce cell arrest and changes in cell cycle status. This is associated with inhibition of pRB phosphorylation through down-regulation of cyclin D1. These novel findings enhance our current understanding of how PTPRG may contribute to tumorigenesis. ©2008 American Association for Cancer Research.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationCancer Research, 2008, v. 68 n. 19, p. 8137-8145 [How to Cite?]
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-08-0904
dc.identifier.doihttp://dx.doi.org/10.1158/0008-5472.CAN-08-0904
dc.identifier.epage8145
dc.identifier.hkuros173234
dc.identifier.isiWOS:000260029900053
Funding AgencyGrant Number
People's Republic of ChinaHKUST6112/04M
Swedish Cancer Society
Swedish Research Council
Swedish Institute
Royal Swedish Academy of Sciences
Karohnska Institute
Funding Information:

Grant support: Research Grants Council of the Hong Kong Special Administrative Region, People's Republic of China grant HKUST6112/04M (M.L. Lung), and Swedish Cancer Society, Swedish Research Council, Swedish Institute, Royal Swedish Academy of Sciences, and Karohnska Institute (E.R. Zabarovsky).

dc.identifier.issn0008-5472
2011 Impact Factor: 7.856
2011 SCImago Journal Rankings: 1.309
dc.identifier.issue19
dc.identifier.pmid18829573
dc.identifier.scopuseid_2-s2.0-54249092901
dc.identifier.spage8137
dc.identifier.urihttp://hdl.handle.net/10722/91259
dc.identifier.volume68
dc.languageeng
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
dc.publisher.placeUnited States
dc.relation.ispartofCancer Research
dc.relation.referencesReferences in Scopus
dc.subject.meshAnimals
dc.subject.meshCarcinoma - genetics
dc.subject.meshCells, Cultured
dc.subject.meshChromosomes, Human, Pair 3
dc.subject.meshDNA Methylation
dc.subject.meshFemale
dc.subject.meshGene Expression Profiling
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshGenes, Tumor Suppressor - physiology
dc.subject.meshGenes, cdc - physiology
dc.subject.meshHumans
dc.subject.meshLoss of Heterozygosity
dc.subject.meshMice
dc.subject.meshMice, Inbred BALB C
dc.subject.meshMice, Nude
dc.subject.meshNasopharyngeal Neoplasms - genetics
dc.subject.meshOligonucleotide Array Sequence Analysis
dc.subject.meshReceptor-Like Protein Tyrosine Phosphatases, Class 5 - genetics - physiology
dc.subjectMolecular Sequence Numbers
dc.titleFunctional analysis of a cell cycle-associated, tumor-suppressive gene, protein tyrosine phosphatase receptor type G, in nasopharyngeal carcinoma
dc.typeArticle
Author Affiliations
  1. Karolinska University Hospital
  2. Sun Yat-Sen University Cancer Center
  3. The University of Hong Kong
  4. Genome Institute of Singapore
  5. City of Hope National Med Center
  6. UC Irvine
  7. Hong Kong University of Science and Technology