Linked Life Data

17538946

Source:http://linkedlifedata.com/resource/pubmed/id/17538946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2007-9-25
pubmed:abstractText
The RASSF1A tumor suppressor is involved in regulation of apoptosis and cell cycle progression. RASSF1A is localized to microtubules and binds the apoptotic kinases MST1 and MST2. It has been shown that this interaction is mediated by the Sav-RASSF-Hpo domain, which is an interaction domain characterized for the Drosophila proteins Sav (human WW45), Hpo (human MST1 and MST2) and Warts/LATS (large tumor suppressor). Previously, we have reported that RASSF1A hypermethylation occurs frequently in soft tissue sarcoma and is associated with an unfavorable prognosis for cancer patients. In our study, we performed methylation analysis of the CpG island promoter of MST1, MST2, WW45, LATS1 and LATS2 in soft tissue sarcomas by methylation-specific PCR. No or a very low methylation frequency was detected for WW45, LATS1 and LATS2 (<7%). In 19 out of 52 (37%) sarcomas, a methylated promoter of MST1 was detected and 12 out of 60 (20%) samples showed methylation of the MST2 promoter. Methylation status of MST1 was confirmed by bisulfite sequencing. In tumors harboring a methylated promoter of MST1, a reduction of MST1 expression was observed by RT-PCR. In leiomyosarcomas, MST1 and MST2 or RASSF1A methylation were mutually exclusive (P = 0.007 and P = 0.025, respectively). Surprisingly, a significantly increased risk for tumor-related death was found for patients with an unmethylated MST1 promoter (P = 0.036). In summary, our results suggest that alteration of the Sav-RASSF1-Hpo tumor suppressor pathway may occur through hypermethylation of the CpG island promoter of MST1, MST2 and/or RASSF1A in human sarcomas.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0899-1987
pubmed:author
pubmed:copyrightInfo
2007 Wiley-Liss, Inc
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
865-71
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Frequent hypermethylation of MST1 and MST2 in soft tissue sarcoma.
pubmed:affiliation
AWG Tumor Genetics of the Medical Faculty, Martin-Luther-University Halle-Wittenberg, Magdeburger Strasse 2, Halle/Saale, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural