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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-7-12
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
689-96
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2002
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.
pubmed:affiliation
Centre Recherche Pathologies Prostatiques-Equipe Accucil 3104 (CeReP-EA), Evry, France. a.latil@urogene.com
pubmed:publicationType
Journal Article