Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2004-8-26
pubmed:abstractText
Secreted frizzled-related proteins (sFRPs) comprise a family of five secreted glycoproteins that antagonize Wnt signaling. Aberrant activation and upregulation of the Wnt pathway is a key feature of many cancers. Thus, role of sFRP as a negative regulator of Wnt signaling may have important implications in tumorigenesis, and its downregulation has been correlated with human cancers. Recently, we reported Wnt signaling and dishevelled (Dvl) overexpression in malignant pleural mesothelioma (MM). Here, we report significant transcriptional downregulation of the SFRP gene family in MM primary tissues and cell lines as well as several other cancer cell lines (breast, lung, glioma, and cervical) compared to normal cells. One or more SFRPs were downregulated in approximately 85% (18 of 21) of primary MM tumor specimens compared to normal pleural tissue. Eight of the nine cancer cell lines we examined showed silencing of the SFRP family. Methylation-specific PCR (MSP) analysis showed that SFRP1, SFRP4, and SFRP5 gene promoters are frequently methylated in MM primary tissue (>80%). Furthermore, transfection of the SFRP gene construct into MM cell lines lacking SFRP expression resulted in apoptosis and growth suppression. Our results suggest that methylation silencing of SFRPs may be one of the important mechanisms of aberrant Wnt signaling activation in MM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6672-6
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma.
pubmed:affiliation
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't