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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-3-4
pubmed:abstractText
We have shown recently that SLIT2 has tumor suppressor activity and that it is epigenetically silenced in >40% of lung and breast tumors. In this study, we have analyzed the methylation status of SLIT2 in primary colorectal cancers and matching normal colorectal mucosa. SLIT2 promoter region methylation was found in 23 (72%) of 32 primary colorectal cancers. In contrast, normal colorectal mucosa from the same patients exhibited significantly lower levels of SLIT2 promoter region hypermethylation. SLIT2 methylation was reversed and expression restored by treating colorectal tumor cell lines with the demethylating agent 5-aza-2-deoxycytidine. Loss of heterozygosity at D4S1546 marker, which maps within 100 kb of the SLIT2 gene, was observed in 39% of the methylated tumors. Furthermore, SLIT2 epigenetic silencing was independent of ROBO1/p16/RASSF1A hypermethylation. The presence of SLIT2 methylation was also independent of the presence of K-RAS mutations. Ectopic expression of SLIT2 diminished the ability to form colonies in two colorectal tumor cell lines. In addition, conditioned medium from SLIT2-transfected COS-7 cells reduced cell growth and induced apoptosis in SW48 colorectal tumor cell line. In conclusion, SLIT2 is an excellent candidate tumor suppressor gene for colorectal cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1054-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12615722-Apoptosis, pubmed-meshheading:12615722-Base Sequence, pubmed-meshheading:12615722-Cell Division, pubmed-meshheading:12615722-Colorectal Neoplasms, pubmed-meshheading:12615722-DNA Methylation, pubmed-meshheading:12615722-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12615722-Gene Silencing, pubmed-meshheading:12615722-Genes, Tumor Suppressor, pubmed-meshheading:12615722-Genes, p16, pubmed-meshheading:12615722-Genes, ras, pubmed-meshheading:12615722-Humans, pubmed-meshheading:12615722-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:12615722-Molecular Sequence Data, pubmed-meshheading:12615722-Neoplasm Proteins, pubmed-meshheading:12615722-Nerve Tissue Proteins, pubmed-meshheading:12615722-Promoter Regions, Genetic, pubmed-meshheading:12615722-Receptors, Immunologic, pubmed-meshheading:12615722-Tumor Suppressor Proteins
pubmed:year
2003
pubmed:articleTitle
SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells.
pubmed:affiliation
Section of Medical and Molecular Genetics, Division of Reproductive and Child Health, University of Birmingham, Birmingham B15 2TT, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't