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dc.contributor.authorEason, Renea R.
dc.contributor.authorTill, S. Renee
dc.contributor.authorFrank, Julie A.
dc.contributor.authorBadger, Thomas M.
dc.contributor.authorKorourian, Sohelia
dc.contributor.authorSimmen, Frank A.
dc.contributor.authorSimmen, Rosalia C.M.
dc.date.accessioned2009-03-06T09:57:43Z
dc.date.available2009-03-06T09:57:43Z
dc.date.issued2006
dc.identifier.citationNutr. Cancer 2006, 55 (2):171-177.en
dc.identifier.issn0163-5581
dc.identifier.pmid17044772
dc.identifier.doi10.1207/s15327914nc5502_8
dc.identifier.urihttp://hdl.handle.net/10146/52513
dc.descriptionDietary modulation of cancer & cancer biomarkers; Dietary modulation of carcinogenesis-related pathways. Dietary item or component studied: whey protein hydrolysate (WPH)Outcome studied: mammary tumor incidence; tumor suppressor BRCA1 gene expression; tumor differentiation marker kappa-casein gene expressionStudy type: female Sprague-Dawley rats Tissue/biological material/sample size: mammary glandsMode of exposure: dietaryImpact on outcome (including dose-response): lifetime exposure to WPH, relative to CAS, decreased mammary tumor incidence and prolonged the appearance of tumors in NMU-treated female rats, with no corresponding effects on tumor multiplicity. At 115 days post-NMU, histologically normal mammary glands from WPH-fed tumor-bearing rats had increased gene expression for the tumor suppressor BRCA1 and the differentiation marker kappa-casein than those of CAS-fed tumor-bearing rats. Tumor-bearing rats from the WPH group had more advanced tumors, with a greater incidence of invasive ductal carcinoma than ductal carcinoma in situ and higher serum C-peptide levels than corresponding rats fed CAS. WPH-fed tumor-bearing rats were also heavier after NMU administration than CAS tumor-bearing rats, although no correlation was noted between body weight and C-peptide levels for either diet group. Keywords - classifications: 9,10-Dimethyl-1,2-benzanthracene;administration & dosage;Animals;Anticarcinogenic Agents;Caseins;Cell Differentiation;dietary modulation of cancer & cancer biomarkers;dietary modulation of carcinogenesis-related pathways;Disease Models,Animal;drug effects;epidemiology;Female;genetic;Genetic Predisposition to Disease;genetics;Humans;Mammary Glands,Animal;Mammary Neoplasms,Experimental;mechanisms of carcinogenesis;metabolism;Milk Proteins;pathology;pharmacology;Pregnancy;Prenatal Exposure Delayed Effects;prevention & control;Proliferating Cell Nuclear Antigen;Proteins;Random Allocation;Rats;Rats,Sprague-Dawley;Research;RNA,Messenger;toxicity;en
dc.description.abstractThe mammary tumor-protective effects of dietary factors are considered to be mediated by multiple signaling pathways, consistent with the heterogeneous nature of the disease and the distinct genetic profiles of tumors arising from diverse mammary cell populations. In a 7,12-dimethylbenz(a)anthracene-induced model of carcinogenesis, we showed previously that female Sprague-Dawley rats exposed to AIN-93G diet containing whey protein hydrolysate (WPH) beginning at gestation Day 4 had reduced tumor incidence than those exposed to diet containing casein (CAS), due partly to increased mammary differentiation and reduced activity of phase I metabolic enzymes. Here, we evaluated the tumor-protective effects of these same dietary proteins to the direct-acting carcinogen N-methyl-N-nitrosourea (NMU). We found that lifetime exposure to WPH, relative to CAS, decreased mammary tumor incidence and prolonged the appearance of tumors in NMU-treated female rats, with no corresponding effects on tumor multiplicity. At 115 days post-NMU, histologically normal mammary glands from WPH-fed tumor-bearing rats had increased gene expression for the tumor suppressor BRCA1 and the differentiation marker kappa-casein than those of CAS-fed tumor-bearing rats. Tumor-bearing rats from the WPH group had more advanced tumors, with a greater incidence of invasive ductal carcinoma than ductal carcinoma in situ and higher serum C-peptide levels than corresponding rats fed CAS. WPH-fed tumor-bearing rats were also heavier after NMU administration than CAS tumor-bearing rats, although no correlation was noted between body weight and C-peptide levels for either diet group. Results demonstrate the context-dependent tumor-protective and tumor-promoting effects of WPH; provide support for distinct signaling pathways underlying dietary effects on development of mammary carcinoma; and raise provocative questions on the role of diet in altering the prognosis of existing breast tumors.
dc.language.isoenen
dc.relation.urlhttp://www.informaworld.com/smpp/content~content=a785830116~db=all~order=pageen
dc.subject.mesh9,10-Dimethyl-1,2-benzanthracene
dc.subject.meshAnimals
dc.subject.meshAnticarcinogenic Agents
dc.subject.meshCaseins
dc.subject.meshCell Differentiation
dc.subject.meshDisease Models, Animal
dc.subject.meshFemale
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshHumans
dc.subject.meshMammary Glands, Animal
dc.subject.meshMammary Neoplasms, Experimental
dc.subject.meshMilk Proteins
dc.subject.meshPregnancy
dc.subject.meshPrenatal Exposure Delayed Effects
dc.subject.meshProliferating Cell Nuclear Antigen
dc.subject.meshRNA, Messenger
dc.subject.meshRandom Allocation
dc.subject.meshRats
dc.subject.meshRats, Sprague-Dawley
dc.titleTumor-protective and tumor-promoting actions of dietary whey proteins in an N-methyl-N-nitrosourea model of rat mammary carcinogenesis.en
dc.typeArticleen
dc.identifier.journalNutrition and Canceren
html.description.abstractThe mammary tumor-protective effects of dietary factors are considered to be mediated by multiple signaling pathways, consistent with the heterogeneous nature of the disease and the distinct genetic profiles of tumors arising from diverse mammary cell populations. In a 7,12-dimethylbenz(a)anthracene-induced model of carcinogenesis, we showed previously that female Sprague-Dawley rats exposed to AIN-93G diet containing whey protein hydrolysate (WPH) beginning at gestation Day 4 had reduced tumor incidence than those exposed to diet containing casein (CAS), due partly to increased mammary differentiation and reduced activity of phase I metabolic enzymes. Here, we evaluated the tumor-protective effects of these same dietary proteins to the direct-acting carcinogen N-methyl-N-nitrosourea (NMU). We found that lifetime exposure to WPH, relative to CAS, decreased mammary tumor incidence and prolonged the appearance of tumors in NMU-treated female rats, with no corresponding effects on tumor multiplicity. At 115 days post-NMU, histologically normal mammary glands from WPH-fed tumor-bearing rats had increased gene expression for the tumor suppressor BRCA1 and the differentiation marker kappa-casein than those of CAS-fed tumor-bearing rats. Tumor-bearing rats from the WPH group had more advanced tumors, with a greater incidence of invasive ductal carcinoma than ductal carcinoma in situ and higher serum C-peptide levels than corresponding rats fed CAS. WPH-fed tumor-bearing rats were also heavier after NMU administration than CAS tumor-bearing rats, although no correlation was noted between body weight and C-peptide levels for either diet group. Results demonstrate the context-dependent tumor-protective and tumor-promoting effects of WPH; provide support for distinct signaling pathways underlying dietary effects on development of mammary carcinoma; and raise provocative questions on the role of diet in altering the prognosis of existing breast tumors.


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