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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #195899
Title: Tumor-Protective and Tumor-Promoting Actions of Dietary Whey Proteins in an N-Methyl-N-Nitrosourea Model of Rat Mammary Carcinogenesis

Author
item EASON, RENEA - ACNC
item TILL, RENEE - ACNC
item FRANK, JULIE - ACNC
item BADGER, THOMAS - ACNC/UAMS
item SIMMEN, FRANK - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS

Submitted to: Nutrition and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/15/2006
Publication Date: 9/15/2006
Citation: Eason, R., Till, R.S., Frank, J.A., Badger, T.M., Simmen, F.A., Simmen, R.C. 2006. Tumor-protective and Tumor-promoting actions of dietary whey proteins in an N-methyl-N-nitrosourea model of rat mammary carcinogenesis. Nutrition and Cancer. 55(2):171-177.

Interpretive Summary: Diet is a risk factor for mammary cancer. In this study we showed that lifetime dietary exposure to whey proteins can have positive and negative effects on mammary tumor susceptibility depending on physiological (health) status. Rats lifetime exposed to whey protein diets have decreased tumor incidence when subjected to carcinogenic insult. However, for those animals that developed tumors, continuous dietary intake of whey proteins increased tumor grade to more invasive status. Results suggest that diet may have a role in altering the prognosis of existing breast tumors.

Technical Abstract: The 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 age 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 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 '-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 (IDC) than ductal carcinoma in situ (DCIS), 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.