Linked Life Data

9849489

Source:http://linkedlifedata.com/resource/pubmed/id/9849489

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1998-12-16
pubmed:abstractText
8-Chloroadenosine 3',5'-monophosphate (8-Cl-cAMP), a site-selective cyclic adenosine 3',5'-monophosphate (cAMP) analogue, exhibits growth inhibition in a broad spectrum of cancer cell lines. We investigated the effect of 8-Cl-cAMP on c-ras-transformed mouse fibroblasts (MP3/3T3) which were established by transfection of Balb3T3 cells (Balb3T3) with the point-mutated c-ras gene [G12-->V12]. 8-Cl-cAMP (2-5 microM) exerted over 80% growth inhibition by day 4 on MP3/3T3, while inhibiting parental Balb3T3 cell growth less than 40%. In order to distinguish the effect of 8-Cl-cAMP from that of 8-chloroadenosine (8-Cl-adenosine), we examined the effect of 8-Cl-cAMP in serum-free medium. 8-Cl-cAMP demonstrated a potent growth inhibition of MP3/3T3 cells cultured in serum-free medium, suggesting that the growth inhibitory effect of 8-Cl-cAMP was not due to its hydrolysed product, 8-Cl-adenosine. In addition, both Balb3T3 and MP3/3T3 contained cAMP phosphodiesterases mainly composed of isozyme IV which has previously been reported to be insensitive towards the hydrolysis of 8-Cl-cAMP. Non-transformed Balb3T3 cells contained only type II cAMP-dependent protein kinase (PKA), whereas transformed MP3/3T3 exhibited a marked increase in type I PKA. The growth inhibition of MP3/3T3 by 8-Cl-cAMP accompanied almost complete elimination of type I PKA without affecting type II PKA. Moreover, 8-Cl-cAMP induced an arrest in the G0/G1-phase of the cell cycle in MP3/3T3. 8-Cl-adenosine had little or no effect on the cell cycle kinetics of MP3/3T3 cells. These results show that 8-Cl-cAMP is a novel cAMP analogue which selectively eliminates type I PKA to induce growth inhibition in transformed fibroblasts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0959-8049
pubmed:author
pubmed:issnType
Print
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1260-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) selectively eliminates protein kinase A type I to induce growth inhibition in c-ras-transformed fibroblasts.
pubmed:affiliation
Cellular Biochemistry Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1750, USA.
pubmed:publicationType
Journal Article