Linked Life Data

11753685

Source:http://linkedlifedata.com/resource/pubmed/id/11753685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
55
pubmed:dateCreated
2001-12-25
pubmed:abstractText
The regulatory (R) subunits of cAMP-dependent protein kinase (PKA) are implicated in the regulation of cell proliferation and differentiation. There are two isoforms of PKA that are distinguished by two types of R subunit, RI and RII. Evidence suggests that RI is associated with proliferation and RII is associated with cell differentiation. Previous work in this laboratory has demonstrated that depletion of the RIalpha subunit by treatment with an antisense oligonucleotide (ODN) induces differentiation in leukemia cells and growth arrest and apoptosis in epithelial cancer cells. Using the prostate cancer cell line PC3M as a model system, we have developed a cell line that overexpresses a retroviral vector construct containing the RIalpha antisense gene. This cell line has been characterized and the effectiveness of the construct determined. In the work presented here, we demonstrate by immunocytochemistry that treatment with RIalpha antisense ODN induces translocation of the Calpha subunit of PKA to the nucleus of PC3M prostate cancer cells. The translocation of Calpha triggered by exogenous antisense ODN treatment mirrors that observed in cells endogenously overexpressing the antisense gene. Triggering the nuclear translocation of the Calpha subunit of PKA in the cell may be an important mechanism of action of RIalpha antisense that regulates cell growth independent of adenylate cyclase and cellular cAMP levels. The nuclear localization of the Calpha subunit of PKA may be an essential step in revealing the mechanism whereby this critical kinase regulates cell growth.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
29
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8019-24
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Nuclear translocation of the catalytic subunit of protein kinase A induced by an antisense oligonucleotide directed against the RIalpha regulatory subunit.
pubmed:affiliation
Cellular Biochemistry Section, Basic Research Laboratories, The Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892-1750, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.