| Dietary olive oil and corn oil differentially affect experimental breast cancer through distinct modulation of the p21Ras signaling and the proliferation-apoptosis balance. | |
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MedLine Citation:
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PMID: 19825967 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Extra-virgin olive oil (EVOO) has been hypothesized to have chemopreventive effects on breast cancer, unlike high corn oil (HCO) diets that stimulate it. We have investigated mechanisms of these differential modulatory actions on experimental mammary cancer. In 7,12-dimethylbenz(a)anthracene adenocarcinomas of rats fed a high EVOO, HCO and control diets (n = 20 for each group), we have analyzed the expression and activity of ErbB receptors, p21Ras and its extracellular signal-regulated kinase (ERK) 1/2, Akt and RalA/B effectors by immunoblotting analyses. We explored the Ha-ras1 mutation status by Southern blot, mismatch amplification mutation assay and sequencing, and the 3-hydroxy-3-methylglutaryl-coenzyme A reductase and squalene synthase messenger RNA expression by real-time polymerase chain reaction. We analyzed the tumor mitotic index, proliferating cell nuclear antigen (PCNA) levels, and apoptosis through Caspase-3 analysis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assays. Finally, we measured the 8-oxo-2'-deoxyguanosine levels. Non-parametrical statistics were used. The EVOO diet decreased Ras activation, downregulated the Ras/phosphatidyl inositol 3-kinase/Akt pathway and upregulated the Raf/Erk pathway, compared with the control. In contrast, the HCO diet did not modify Ras activity but rather enhanced the Raf/Erk pathway. The EVOO diet decreased the cleaved ErbB4 levels, compared with the HCO diet, increased apoptosis and diminished the mono-ubiquitylated PCNA levels, which is related to DNA damage. Tumors from rats fed the EVOO diet displayed a more benign phenotype, whereas those from rats fed the HCO diet were biologically more aggressive. In conclusion, high EVOO and corn oil diets exert their modulatory effects on breast cancer through a different combination of Ras signaling pathways, a different proliferation-apoptosis balance and probably distinct levels of DNA damage. |
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Authors:
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Montserrat Solanas; Laura Grau; Raquel Moral; Elena Vela; Raquel Escrich; Eduard Escrich |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-13 |
Journal Detail:
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Title: Carcinogenesis Volume: 31 ISSN: 1460-2180 ISO Abbreviation: Carcinogenesis Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-06 Completed Date: 2010-05-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008055 Medline TA: Carcinogenesis Country: England |
Other Details:
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Languages: eng Pagination: 871-9 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, Physiology and Immunology, Medical Physiology Unit, Medicine School, Universitat Aut?noma de Barcelona 08193 Bellaterra, Barcelona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Cell Proliferation / drug effects Corn Oil / pharmacology* Deoxyguanosine / analogs & derivatives, analysis Extracellular Signal-Regulated MAP Kinases / physiology Female Mammary Neoplasms, Experimental / chemically induced*, pathology Mutation Plant Oils / pharmacology* Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins p21(ras) / analysis, physiology* Rats Rats, Sprague-Dawley Receptor, erbB-2 / analysis Signal Transduction / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Plant Oils; 8001-25-0/olive oil; 8001-30-7/Corn Oil; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 961-07-9/Deoxyguanosine; EC 2.7.10.1/Receptor, erbB-2; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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