| Reversion of transformed phenotype of human adenocarcinoma A549 cells by expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase complementary DNA. | |
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MedLine Citation:
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PMID: 8562480 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S Seronie-Vivien; A Pradines; B Couderc; C Clamagirand; D Berg; G Soula; G Favre |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research Volume: 6 ISSN: 1044-9523 ISO Abbreviation: Cell Growth Differ. Publication Date: 1995 Nov |
Date Detail:
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Created Date: 1996-03-04 Completed Date: 1996-03-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9100024 Medline TA: Cell Growth Differ Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1415-23 Citation Subset: IM |
Affiliation:
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Laboratoire de Ciblage en Thérapeutique, UFR des Sciences Pharmaceutiques, Toulose, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acyl Coenzyme A
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genetics*,
metabolism Adenocarcinoma / enzymology* Agar Animals Cell Division / physiology Cell Line, Transformed Cloning, Molecular Cytoskeleton / enzymology DNA, Complementary / genetics Humans Kinetics Lung Neoplasms Mice Mice, Nude Oxidoreductases / genetics, metabolism Phenotype RNA, Messenger / analysis Transformation, Genetic Tumor Cells, Cultured / cytology, enzymology |
| Chemical | |
Reg. No./Substance:
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0/Acyl Coenzyme A; 0/DNA, Complementary; 0/RNA, Messenger; 1553-55-5/3-hydroxy-3-methylglutaryl-coenzyme A; 9002-18-0/Agar; EC 1.-/Oxidoreductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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