Linked Life Data

11062168

Source:http://linkedlifedata.com/resource/pubmed/id/11062168

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-12-6
pubmed:abstractText
p14(ARF) is a putative tumor suppressor gene thought to modify the levels of p53. CpG sites within the 5'-flanking region and exon 1beta of p14(ARF) are targets of aberrant methylation and transcriptional silencing in human colorectal cancer (CRC). Here we have developed methylation-specific polymerase chain reaction (MSPCR) methods to detect methylation of CpG sites in p14(ARF) in CRC cell lines and primary CRC tumors, and correlated p14(ARF) mRNA expression with methylation in CRC cell lines using competitive quantitative reverse transcription-polymerase chain reaction methods. Ten CRC cell lines were studied; three (DLD-1, HCT15 and SW48) showed extensive methylation and six (Colo320, SW480, HT29, Caco2, SW837 and WiDr) were unmethylated; the other cell line, LoVo, showed partial methylation that affected exon 1beta but not the immediate upstream CpG sites. p14(ARF) mRNA was expressed at extremely low levels in fully methylated cell lines and at 10(4)- to 10(5)-fold higher levels in unmethylated cell lines. p14(ARF) expression in the partially methylated LoVo cell line was intermediate. Treatment of LoVo cells with 2 microM 5-aza-2'-deoxycytidine for 72 h was associated with marked (100-fold) induction of mRNA levels. Of 119 primary CRCs, 18% contained p14(ARF) methylation, although partial methylation was the most common pattern observed (in 67% of methylated tumors). Methylation of p14(ARF) was often accompanied by p16(INK4a) methylation; however, 50% of p14(ARF) methylated tumors contained unmethylated p16(INK4a). Methylation at p14(ARF) was associated with female gender, greater age, proximal anatomic location and poor differentiation, but not stage at diagnosis. A two-step MSPCR method for assaying p14(ARF) methylation in human tumors is described.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2057-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11062168-Adult, pubmed-meshheading:11062168-Aged, pubmed-meshheading:11062168-Aged, 80 and over, pubmed-meshheading:11062168-Base Sequence, pubmed-meshheading:11062168-Colorectal Neoplasms, pubmed-meshheading:11062168-CpG Islands, pubmed-meshheading:11062168-DNA, Neoplasm, pubmed-meshheading:11062168-DNA Methylation, pubmed-meshheading:11062168-Exons, pubmed-meshheading:11062168-Female, pubmed-meshheading:11062168-Humans, pubmed-meshheading:11062168-Male, pubmed-meshheading:11062168-Middle Aged, pubmed-meshheading:11062168-Molecular Sequence Data, pubmed-meshheading:11062168-Polymerase Chain Reaction, pubmed-meshheading:11062168-Proteins, pubmed-meshheading:11062168-RNA, Messenger, pubmed-meshheading:11062168-Sequence Analysis, DNA, pubmed-meshheading:11062168-Sulfites, pubmed-meshheading:11062168-Tumor Cells, Cultured, pubmed-meshheading:11062168-Tumor Suppressor Protein p14ARF
pubmed:year
2000
pubmed:articleTitle
Correlations of partial and extensive methylation at the p14(ARF) locus with reduced mRNA expression in colorectal cancer cell lines and clinicopathological features in primary tumors.
pubmed:affiliation
Laboratory for Molecular Epidemiology, Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143-0560, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't