Linked Life Data

8562480

Source:http://linkedlifedata.com/resource/pubmed/id/8562480

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1996-3-4
pubmed:abstractText
3-Hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) plays a rate-limiting role in isoprenoid biosynthesis and is associated with cell proliferation and transformation. Although an elevated level of HMG-CoA reductase activity is consistently detected in cancer cell lines and tumors, the question remains whether HMG-CoA reductase activity may have a causative role in cell transformation. We have stably transfected the A549 human adenocarcinoma cells with both bicistronic and retroviral expression vectors, including the whole cDNA of human HMG-CoA reductase. Stably transfected cells showed strong morphological changes and disorganization in the filamentous actin architecture, became contact inhibited, and had a lower doubling time. Moreover, they exhibited anchorage-independent growth reduction and lost their capability to induce tumors in nude mice. Surprisingly, no quantitative modification of enzyme activity was observed following transfection, although expression of HMG-CoA reductase cDNA was shown by Northern blot analysis. When endogenous and transfected reductase activity was bypassed by the addition of mevalonate and compactin, a competitive inhibitor, the filamentous actin distribution in HMG-CoA reductase-transfected cells became very similar to that of control cells, demonstrating the role of exogenous HMG-CoA reductase activity in this process. All of our data together strongly suggest that phenotype reversion is dependent on exogenous HMG-CoA reductase expression and that enzymatic activity is implied in this mechanism. HMG-CoA reductase cDNA expression, by expression of a particular form of reductase, might be a negative regulator of cell growth and thus reverse the phenotype of tumor cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1415-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Reversion of transformed phenotype of human adenocarcinoma A549 cells by expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase complementary DNA.
pubmed:affiliation
Laboratoire de Ciblage en Thérapeutique, UFR des Sciences Pharmaceutiques, Toulose, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't