Linked Life Data

11198926

Source:http://linkedlifedata.com/resource/pubmed/id/11198926

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-1-26
pubmed:abstractText
The primary mediator of cAMP action in mammalian cells is cAMP-dependent protein kinase (PKA). There are two types of PKA, type I (PKA-I) and type II (PKA-II), which share a common catalytic subunit but contain distinct regulatory subunits, RI and RII, respectively. Evidence suggests that increased expression of RIalpha/PKA-I correlates with neoplastic cell growth. Here, we show that sequence-specific oligonucleotide inhibition of RIalpha expression results in inhibition of growth and modulation of cAMP signaling in cancer cells. The antisense promoted growth inhibition in a time-dependent, concentration-dependent, and sequence-dependent manner in human cancer cells in monolayer culture, and it inhibited colony formation in soft agar and tumor growth in nude mice. Among the cancer cells are LS-174T, HCT-15, and Colo-205 colon carcinoma cells; A-549 lung carcinoma cells; LNCaP prostate adenocarcinoma cells; Molt-4 leukemia cells; and Jurkat T lymphoma cells. Northern blot and immunoprecipitation analyses revealed that the growth inhibitory effect of the antisense correlated with a decrease in RIalpha expression at both the mRNA and protein levels. Pulse-chase experiments revealed that the antisense-directed inhibition of RIalpha expression resulted in compensatory changes in expression of the isoforms of R and C subunits and cAMP signaling in a cell type-specific manner. These results demonstrate that cAMP is ubiquitous in the regulation of cell growth and that the antisense oligonucleotide, which inhibits the synthesis of the RIalpha subunit of PKA, can be targeted to a single gene for treatment of cancer in a variety of cell types.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1087-2906
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-33
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11198926-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:11198926-3' Untranslated Regions, pubmed-meshheading:11198926-Biological Transport, pubmed-meshheading:11198926-Cell Division, pubmed-meshheading:11198926-Cyclic AMP, pubmed-meshheading:11198926-Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, pubmed-meshheading:11198926-Cyclic AMP-Dependent Protein Kinase Type II, pubmed-meshheading:11198926-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:11198926-DNA, Antisense, pubmed-meshheading:11198926-Enzyme Stability, pubmed-meshheading:11198926-Gene Expression, pubmed-meshheading:11198926-Gene Targeting, pubmed-meshheading:11198926-Humans, pubmed-meshheading:11198926-Oligonucleotides, Antisense, pubmed-meshheading:11198926-RNA, Antisense, pubmed-meshheading:11198926-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Oligonucleotide sequence-specific inhibition of gene expression, tumor growth inhibition, and modulation of cAMP signaling by an RNA-DNA hybrid antisense targeted to protein kinase A RIalpha subunit.
pubmed:affiliation
Cellular Biochemistry Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1750, USA.
pubmed:publicationType
Journal Article