Source:http://linkedlifedata.com/resource/pubmed/id/12115502
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2002-7-12
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pubmed:abstractText |
Loss of heterozygosity (LOH) at chromosome 13q14 is one of the most recurrent anomalies observed in sporadic prostate tumors. This LOH is believed to unmask recessive mutations that inactivate a tumor-suppressor gene(s) which otherwise regulates normal cell growth and suppresses abnormal cell proliferation. Identification of potential tumor-suppressor genes within the deleted region is a way of indicating putative pathways of prostate cancer development and progression. The main target that disappears or is downregulated as a result of 13q14 loss remains to be identified. Therefore, our first concern was to find a gene located in the 13q14 region whose transcription is reduced. CHC1-L, for chromosome condensation 1-like, is mapped to the smallest common deleted region. CHC1-L expression is significantly reduced in prostate tumors compared to normal prostate tissues (p = 0.0002). In 21 of 36 (58%) primary prostate tumors studied, CHC1-L expression was reduced at least 2-fold, as measured by real-time quantitative RT-PCR; 18 of the tumors (50%) showed 13q14 LOH for at least 1 of the 5 polymorphic markers that we studied in the region, and 14 (78%) of these were among the tumors underexpressing CHC1-L. CHC1-L is alternatively spliced at its 5' end to produce 2 isoforms, of 551 and 526 aa. Analyses of CHC1-L integrity and of the quantitative expression of its variants indicate that the observed underexpression in prostate tumors is related to reduced expression of the 551 aa isoform. Although CHC1-L is not the obvious candidate given its only known homology, to RCC1, a guanine nucleotide exchange factor for the Ras-related GTPase Ran, the frequent significant decrease observed in its expression in prostate cancer associated with the difference in frequency of CHC1-L variant isoforms between normal and neoplastic prostate tissues places it in a pivotal role or possibly adjacent to a gene that has that role in prostate cancer evolution.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2002 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
99
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
689-96
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:12115502-Alleles,
pubmed-meshheading:12115502-Alternative Splicing,
pubmed-meshheading:12115502-Chromosomes, Human, Pair 13,
pubmed-meshheading:12115502-DNA, Neoplasm,
pubmed-meshheading:12115502-Gene Expression,
pubmed-meshheading:12115502-Humans,
pubmed-meshheading:12115502-Loss of Heterozygosity,
pubmed-meshheading:12115502-Male,
pubmed-meshheading:12115502-Neoplasm Proteins,
pubmed-meshheading:12115502-Neoplasm Staging,
pubmed-meshheading:12115502-Polymerase Chain Reaction,
pubmed-meshheading:12115502-Prostate,
pubmed-meshheading:12115502-Prostatic Neoplasms,
pubmed-meshheading:12115502-RNA, Messenger,
pubmed-meshheading:12115502-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12115502-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
CHC1-L, a candidate gene for prostate carcinogenesis at 13q14.2, is frequently affected by loss of heterozygosity and underexpressed in human prostate cancer.
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pubmed:affiliation |
Centre Recherche Pathologies Prostatiques-Equipe Accucil 3104 (CeReP-EA), Evry, France. a.latil@urogene.com
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pubmed:publicationType |
Journal Article
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