Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-6-2
pubmed:abstractText
By using a functional complementation approach, suppression of tumorigenicity was observed after transfer of intact or truncated copies of chromosome 3 into a nasopharyngeal carcinoma (NPC) HONE1 cell line. The extra exogenous chromosome 3 in the microcell hybrids (MCHs) significantly extended the lag period of tumor formation, which may be associated with loss or inactivation of wild type alleles from the normal donor chromosome 3. Representative tumors, which grew in nude mice were reconstituted into culture and expanded as tumor segregants (TSs). In our study, a disintegrin-like and metalloprotease with thrombospondin type 1 motif 9 (ADAMTS9), a gene mapping to 3p14.2, was identified to be critically associated with tumor suppression in NPC. Gene expression analysis showed that ADAMTS9 was either not expressed or was downregulated in HONE1 cells, TSs and NPC cell lines. The mechanism of ADAMTS9 gene inactivation in the NPC cell lines and tissues was attributed to promoter hypermethylation. Using a tissue microarray and immunohistochemical staining, 31 of 66 (47%) of the NPC cases showed downregulated or absence of ADAMTS9 expression. ADAMTS9 expression was downregulated or lost in 17 of 23 (73.9%) lymph node metastatic NPC specimens, which was significantly higher than in 14 of 43 (32.6%) primary tumors. After transfection of the ADAMTS9 gene into 7 NPC cell lines, a dramatic reduction of colony forming ability was observed. These findings support ADAMTS9 as a putative tumor suppressor gene in vivo in NPC that is significantly associated with lymph node metastases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-0215
pubmed:author
pubmed:copyrightInfo
(c) 2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
123
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
401-8
pubmed:meshHeading
pubmed-meshheading:18449890-ADAM Proteins, pubmed-meshheading:18449890-Adult, pubmed-meshheading:18449890-Aged, pubmed-meshheading:18449890-Carcinoma, pubmed-meshheading:18449890-Chromosomes, Human, Pair 3, pubmed-meshheading:18449890-Down-Regulation, pubmed-meshheading:18449890-Female, pubmed-meshheading:18449890-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18449890-Gene Silencing, pubmed-meshheading:18449890-Genotype, pubmed-meshheading:18449890-Humans, pubmed-meshheading:18449890-Immunohistochemistry, pubmed-meshheading:18449890-Lymph Nodes, pubmed-meshheading:18449890-Lymphatic Metastasis, pubmed-meshheading:18449890-Male, pubmed-meshheading:18449890-Microarray Analysis, pubmed-meshheading:18449890-Microsatellite Repeats, pubmed-meshheading:18449890-Middle Aged, pubmed-meshheading:18449890-Nasopharyngeal Neoplasms, pubmed-meshheading:18449890-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18449890-Tumor Markers, Biological
pubmed:year
2008
pubmed:articleTitle
Characterization of a novel epigenetically-silenced, growth-suppressive gene, ADAMTS9, and its association with lymph node metastases in nasopharyngeal carcinoma.
pubmed:affiliation
Department of Biology and Center for Cancer Research, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (SAR), People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural