| Activation of Stat5 and induction of a pregnancy-like mammary gland differentiation by eicosapentaenoic and docosapentaenoic omega-3 fatty acids. | |
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MedLine Citation:
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PMID: 17547694 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The protective effect of early pregnancy against breast cancer can be attributed to the transition from undifferentiated cells in the nulliparous to the differentiated mature cells during pregnancy. Considerable evidence suggests strongly that the n-3 polyunsaturated fatty acid (PUFA) content of adipose breast tissue is inversely associated with an increased risk of breast cancer. Here, we report that there was a decrease in the n-6/n-3 PUFA ratio and a significant increase in concentration of n-3 PUFA docosapentaenoic acid and eicosapentaenoic acid in the pregnant gland. The functional role of n-3 PUFAs on differentiation was supported by the studies in the fat-1 transgenic mouse, which converts endogenous n-6 to n-3 PUFAs. Alternation of the n-6/n-3 ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid, in the mammary gland of fat-1 mouse resulted in development of lobulo-alveolar-like structure and milk protein beta-casein expression, mimicking the differentiated state of the pregnant gland. Docosapentaenoic acid and eicosapentaenoic acid activated the Jak2/Stat5 signaling pathway and induced a functional differentiation with production of beta-casein. Expression of brain type fatty acid binding protein brain type fatty acid binding protein in virgin transgenic mice also resulted in a reduced ratio of n-6/n-3 PUFA, a robust increase in docosapentaenoic acid accumulation, and mammary differentiation. These data indicate a role of mammary derived growth inhibitor related gene for preferential accumulation of n-3 docosapentaenoic acid and eicosapentaenoic acid in the differentiated gland during pregnancy. Thus, alternation of n-6/n-3 fatty acid compositional ratio in favor of n-3 PUFA, and particularly docosapentaenoic acid and eicosapentaenoic acid, is one of the underlying mechanisms of pregnancy-induced mammary differentiation. |
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Authors:
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Yiliang E Liu; Weiping Pu; Jingdong Wang; Jing X Kang; Y Eric Shi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2007-06-05 |
Journal Detail:
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Title: The FEBS journal Volume: 274 ISSN: 1742-464X ISO Abbreviation: FEBS J. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-05 Completed Date: 2007-08-20 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 101229646 Medline TA: FEBS J Country: England |
Other Details:
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Languages: eng Pagination: 3351-62 Citation Subset: IM |
Affiliation:
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Feinstein Institute for Medical Research, Department of Radiation Oncology, Long Island Jewish Medical Center, The Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipose Tissue
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metabolism Animals Eicosapentaenoic Acid / metabolism Fatty Acid-Binding Proteins / genetics* Fatty Acids, Omega-3 / metabolism Fatty Acids, Omega-6 / metabolism Fatty Acids, Unsaturated / metabolism* Female Mammary Glands, Animal / metabolism* Mammary Neoplasms, Animal / metabolism* Mice Mice, Transgenic Pregnancy Pregnancy, Animal* |
| Grant Support | |
ID/Acronym/Agency:
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CA93542-2/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fabp3 protein, mouse; 0/Fatty Acid-Binding Proteins; 0/Fatty Acids, Omega-3; 0/Fatty Acids, Omega-6; 0/Fatty Acids, Unsaturated; 1553-41-9/Eicosapentaenoic Acid; 25448-00-4/docosapentaenoic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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