{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T17:31:54Z","timestamp":1773768714642,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T00:00:00Z","timestamp":1344211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2012,10]]},"abstract":"Abstract<\/jats:title>The prevalence of obesity, an established risk and progression factor for breast and many other cancer types, remains very high in the United States and throughout the world. Calorie restriction (CR<\/jats:styled-content>), a reduced\u2010calorie dietary regimen typically involving a 20\u201340% reduction in calorie consumption, prevents or reverses obesity, and inhibits mammary and other types of cancer in multiple tumor model systems. Unfortunately, the mechanisms underlying the tumor inhibitory effects of CR<\/jats:styled-content> are poorly understood, and a better understanding of these mechanisms may lead to new intervention targets and strategies for preventing or controlling cancer. We have previously shown that the anticancer effects of CR<\/jats:styled-content> are associated with decreased systemic levels of insulin\u2010like growth factor\u20101 (IGF<\/jats:styled-content>\u20101), the primary source of which is liver. We have also reported that CR<\/jats:styled-content> strongly suppresses tumor development and growth in multiple mammary cancer models. To identify CR<\/jats:styled-content>\u2010responsive genes and pathways, and to further characterize the role of IGF<\/jats:styled-content>\u20101 as a mediator of the anticancer effects of CR, we assessed hepatic and mammary gland gene expression, hormone levels and growth of orthotopically transplanted mammary tumors in control and CR<\/jats:styled-content> mice with and without exogenous IGF<\/jats:styled-content>\u20101. C57BL\/6 mice were fed either control AIN\u201076A diet ad libitum (AL<\/jats:styled-content>), subjected to 20%, 30%, or 40% CR<\/jats:styled-content> plus placebo timed\u2010release pellets, or subjected to 30% or 40% CR<\/jats:styled-content> plus timed\u2010release pellets delivering murine IGF<\/jats:styled-content>\u20101 (mIGF<\/jats:styled-content>\u20101, 20\u00a0\u03bc<\/jats:italic>g\/day). Compared with AL<\/jats:styled-content>\u2010fed controls, body weights were decreased 14.3% in the 20% CR<\/jats:styled-content> group, 18.5% in the 30% CR<\/jats:styled-content> group, and 38% in the 40% CR<\/jats:styled-content> group; IGF<\/jats:styled-content>\u20101 infusion had no effect on body weight. Hepatic transcriptome analyses indicated that compared with 20% CR<\/jats:styled-content>, 30% CR<\/jats:styled-content> significantly modulated more than twice the number of genes and 40% CR<\/jats:styled-content> more than seven times the number of genes. Many of the genes specific to the 40% CR<\/jats:styled-content> regimen were hepatic stress\u2010related and\/or DNA<\/jats:styled-content> damage\u2010related genes. Exogenous IGF<\/jats:styled-content>\u20101 rescued the hepatic expression of several metabolic genes and pathways affected by CR<\/jats:styled-content>. Exogenous IGF<\/jats:styled-content>\u20101 also rescued the expression of several metabolism\u2010 and cancer\u2010related genes affected by CR<\/jats:styled-content> in the mammary gland. Furthermore, exogenous IGF<\/jats:styled-content>\u20101 partially reversed the mammary tumor inhibitory effects of 30% CR<\/jats:styled-content>. We conclude that several genes and pathways, particularly those associated with macronutrient and steroid hormone metabolism, are associated with the anticancer effects of CR<\/jats:styled-content>, and that reduced IGF<\/jats:styled-content>\u20101 levels can account, at least in part, for many of the effects of CR<\/jats:styled-content> on gene expression and mammary tumor burden.<\/jats:p>","DOI":"10.1002\/cam4.23","type":"journal-article","created":{"date-parts":[[2012,8,6]],"date-time":"2012-08-06T10:01:07Z","timestamp":1344247267000},"page":"275-288","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Dose\u2010dependent effects of calorie restriction on gene expression, metabolism, and tumor progression are partially mediated by insulin\u2010like growth factor\u20101"],"prefix":"10.1002","volume":"1","author":[{"given":"Leticia M.","family":"Nogueira","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute, NIH Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackie A.","family":"Lavigne","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics National Cancer Institute, NIH Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gadisetti V. R.","family":"Chandramouli","sequence":"additional","affiliation":[{"name":"NCI Center for Bioinformatics\/Science Applications International Corporation Rockville Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaitian","family":"Lui","sequence":"additional","affiliation":[{"name":"Science Applications International Corporation Rockville Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Carl","family":"Barrett","sequence":"additional","affiliation":[{"name":"Translational Sciences for Oncology Innovative Medicines AstraZeneca Pharmaceuticals, Inc. Waltham Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Hursting","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Texas at Austin and Department of Molecular Carcinogenesis UT\u2010MD Anderson Cancer Center Smithville Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp280"},{"key":"e_1_2_7_3_1","unstructured":"World Cancer Research Fund.2007.Food nutrition physical activity and the prevention of cancer: a global perspective.American Institute for Cancer Research Washington DC."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.2014"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1408"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015288615472"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-06-0045"},{"key":"e_1_2_7_8_1","unstructured":"American Cancer Society.2012.Cancer facts & figures 2011\u20132012.American Cancer Society Atlanta."},{"key":"e_1_2_7_9_1","first-page":"667","article-title":"Phenotypic effects of calorie restriction and insulin\u2010like growth factor\u20101 treatment on body composition and bone mineral density of C57BL\/6 mice: implications for cancer prevention","volume":"19","author":"Berrigan D.","year":"2005","journal-title":"In Vivo"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/134.9.2482S"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-11-0027"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20577"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1837"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2536"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-10-0375"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.191313598"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20045"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1118"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635580801966195"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806179200"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(03)00091-3"},{"key":"e_1_2_7_24_1","first-page":"4667","article-title":"Dietary restriction reduces insulin\u2010like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53\u2010deficient mice","volume":"57","author":"Dunn S. E.","year":"1997","journal-title":"Cancer Res."},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.17.3.327"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.132384699"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713680903177890"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004046200"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2004.00142.x"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020239211145"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00203.2003"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0142"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305300101"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00074.2008"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0156"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300996200"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209493200"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311404200"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600095-JLR200"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7827(01)00017-0"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700119-JLR200"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.20.1.42"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27955"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)02100-1"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-09-0034"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2006.05214.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.332"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20071"},{"key":"e_1_2_7_49_1","first-page":"2750","article-title":"The growth hormone: insulin\u2010like growth factor 1 axis is a mediator of diet restriction\u2010induced inhibition of mononuclear cell leukemia in Fischer rats","volume":"53","author":"Hursting S. D.","year":"1993","journal-title":"Cancer Res."},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-2472"},{"key":"e_1_2_7_51_1","first-page":"24","article-title":"Microarray experimental design: power and sample size considerations","volume":"42","author":"Kang M. C. K.","year":"2003","journal-title":"Physiol. Genomics"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-5-research0022"}],"updated-by":[{"DOI":"10.1002\/cam4.7143","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000}}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.23","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.23","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T14:45:26Z","timestamp":1697467526000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,6]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,10]]}},"alternative-id":["10.1002\/cam4.23"],"URL":"https:\/\/doi.org\/10.1002\/cam4.23","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,6]]},"assertion":[{"value":"2012-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-07-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}