Linked Life Data

15258566

Source:http://linkedlifedata.com/resource/pubmed/id/15258566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2004-9-16
pubmed:abstractText
AKAP12/Gravin, one of the A-kinase anchoring proteins (AKAPs), functions as a kinase scaffold protein and as a dynamic regulator of the beta2-adrenergic receptor complex. However, the biological role of AKAP12 in cancer development is not well understood. The AKAP12 gene encodes two major isoforms of 305 and 287 kDa (designated AKAP12A and AKAP12B, respectively, in this report). We found that these two isoforms are independently expressed and that they are probably under the control of two different promoters. Moreover, both isoforms were absent from the majority of human gastric cancer cells. The results from methylation-specific PCR (MSP) and bisulfite sequencing revealed that the 5' CpG islands of both AKAP12A and AKAP12B are frequently hypermethylated in gastric cancer cells. Treatment with DNA methyltransferase inhibitor and/or histone deacetylase inhibitor efficiently restored the expression of AKAP12 isoforms, confirming that DNA methylation is directly involved in the transcriptional silencing of AKAP12 in gastric cancer cells. Hypermethylation of AKAP12A CpG island was also detected in 56% (10 of 18) of primary gastric tumors. The restoration of AKAP12A in AKAP12-nonexpressing cells reduced colony formation and induced apoptotic cell death. In conclusion, our results suggest that AKAP12A may function as an important negative regulator of the survival pathway in human gastric cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7095-103
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
AKAP12/Gravin is inactivated by epigenetic mechanism in human gastric carcinoma and shows growth suppressor activity.
pubmed:affiliation
National Research Laboratory for Cancer Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't