{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:40:56Z","timestamp":1790872856290,"version":"4.1.0"},"reference-count":83,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Choline is an essential nutrient that serves as a donor of metabolic methyl groups used during gestation to establish the epigenetic DNA methylation patterns that modulate tissue\u2010specific gene expression. Because the mammary gland begins its development prenatally, we hypothesized that choline availability\n                    <jats:italic>in utero<\/jats:italic>\n                    may affect the gland's susceptibility to cancer. During gestational days 11\u201317, pregnant rats were fed a control, choline\u2010supplemented, or choline\u2010deficient diet (8, 36, and 0 mmol\/kg of choline, respectively). On postnatal day 65, the female offspring received 25 mg\/kg of a carcinogen 7,12\u2010dimethylbenz[a]anthracene. Approximately 70% of the rats developed mammary adenocarcinomas; prenatal diet did not affect tumor latency, incidence, size, and multiplicity. Tumor growth rate was inversely related to choline content in the prenatal diet, resulting in 50% longer survival until euthanasia, determined by tumor size, of the prenatally choline\u2010supplemented rats compared with the prenatally choline\u2010deficient rats. This was accompanied by distinct expression patterns of ~70 genes in tumors derived from the three dietary groups. Tumors from the prenatally choline\u2010supple\u2010mented rats overexpressed genes that confer favorable prognosis in human cancers (\n                    <jats:italic>Klf6, Kf9, Nid2, Ntn4, Perl<\/jats:italic>\n                    , and\n                    <jats:italic>Txnip<\/jats:italic>\n                    ) and underexpressed those associated with aggressive disease (\n                    <jats:italic>Bcar3, Cldn12, Csfl, Jagl, Lgals3, Lypd3, Nmel, Ptges2, Ptgsl<\/jats:italic>\n                    , and\n                    <jats:italic>Smarcbl)<\/jats:italic>\n                    . DNA methylation within the tumor suppressor gene, stratifin (\n                    <jats:italic>Sfn<\/jats:italic>\n                    , 14\u20103\u20103\u03c3), was proportional to the prenatal choline supply and correlated inversely with the expression of its mRNA and protein in tumors, suggesting that an epigenetic mechanism may underlie the altered molecular phenotype and tumor growth. Our results suggest a role for adequate maternal choline nutrition during pregnancy in prevention\/alleviation of breast cancer in daughters.\u2014Kovacheva, V. P., Davison, J. M., Mellott, T. J., Rogers, A. E., Yang, S., O'Brien, M. J., Blusztajn, J. K. Raising gestational choline intake alters gene expression in DMBA\u2010evoked mammary tumors and prolongs survival.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 23, 1054\u20131063 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-122168","type":"journal-article","created":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T20:54:32Z","timestamp":1228164872000},"page":"1054-1063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Raising gestational choline intake alters gene expression in DMBA\u2010evoked mammary tumors and prolongs survival"],"prefix":"10.1096","volume":"23","author":[{"given":"Vesela P.","family":"Kovacheva","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Davison","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany J.","family":"Mellott","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne E.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Krzysztof","family":"Blusztajn","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-5043-7_3"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91000-Z"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(07)70377-7"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2006.09.002"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.17.9372"},{"key":"e_1_2_5_7_1","first-page":"244","article-title":"Comparative study of human and rat mammary tumorigenesis","volume":"62","author":"Russo J.","year":"1990","journal-title":"Lab. 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