| Ornithine decarboxylase over-expression stimulates mitogen-activated protein kinase and anchorage-independent growth of human breast epithelial cells. | |
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MedLine Citation:
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PMID: 9009157 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In these experiments we tested the hypothesis that constitutive activation of polyamine(PA) biosynthesis may contribute to mammary carcinogenesis. Spontaneously immortalized normal human MCF-10A breast epithelial cells were infected with the retroviral vector pLOSN containing a cDNA which codes for a truncated and more stable ornithine decarboxylase (ODC), the rate-limiting enzyme in PA synthesis. Upon chronic selective pressure with alpha-difluoromethyl-ornithine (DFMO) (an irreversible inhibitor of ODC), infected MCF-10A cells exhibited an approximately 250-fold increase in ODC activity, which persisted despite discontinuation of DFMO. ODC-over-expressing MCF-10A cells showed a modest decrease in S-adenosylmethionine decarboxylase and an increase in spermidine/spermineN1-acetyltransferase. Analysis of cellular PA profile revealed a selective accumulation of putrescine without alterations in spermidine and spermine contents. Lesser degrees of increased ODC activity were obtained reproducibly by re-exposing the cells to incremental small doses of DFMO. We observed a bell-shaped dose-related positive effect of ODC activity on clonogenicity in soft agar of MCF-10A cells. Since anchorage-dependent growth was actually reduced, such positive influence on this feature of transformation was not a non-specific consequence of a growth advantage provided by ODC over-expression. In addition, we observed a close parallelism between the dose-dependent effects of ODC expression on clonogenicity and activity of the ERK-2 kinase, a central element of the MAPK cascade. Our data demonstrate an interaction between PA and the MAPK signalling pathway and suggest that the latter may be involved in ODC-induced transformation of mammary epithelial cells. |
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Authors:
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A Manni; R Wechter; S Gilmour; M F Verderame; D Mauger; L M Demers |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 70 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 1997 Jan |
Date Detail:
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Created Date: 1997-02-20 Completed Date: 1997-02-20 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 175-82 Citation Subset: IM |
Affiliation:
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Department of Medicine, Milton S. Hershey Medical School, Pennsylvania State University, Hershey, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetyltransferases
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metabolism Adenosylmethionine Decarboxylase / metabolism Breast / cytology*, drug effects, enzymology Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Cell Line, Transformed Cell Transformation, Neoplastic / genetics* Colony-Forming Units Assay DNA, Complementary / genetics Eflornithine / pharmacology Enzyme Induction Epithelial Cells Epithelium / drug effects, enzymology Female Genes, ras Humans Mitogen-Activated Protein Kinase 1 Ornithine Decarboxylase / antagonists & inhibitors, biosynthesis, chemistry, genetics, physiology* Polyamines / metabolism Recombinant Fusion Proteins / metabolism Signal Transduction / physiology Transfection |
| Grant Support | |
ID/Acronym/Agency:
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CA40011-11/CA/NCI NIH HHS; R-29CA55066/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/Polyamines; 0/Recombinant Fusion Proteins; 70052-12-9/Eflornithine; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.57/diamine N-acetyltransferase; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 4.1.1.17/Ornithine Decarboxylase; EC 4.1.1.50/Adenosylmethionine Decarboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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