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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #190218
Title: TP53-ASSOCIATED GROWTH ARREST AND DNA DAMAGE REPAIR GENE EXPRESSION IS ATTENUATED IN MAMMARY EPITHELIAL CELLS OF RATS FED WHEY PROTEINS

Author
item DAVE, BHUVANESH - ACNC/UAMS
item EASON, RENEA - ACNC
item GENG, YAN - ACNC/UAMS
item SU, YING - ACNC/UAMS
item BADGER, THOMAS - ACNC/UAMS
item SIMMEN, ROSALIA - ACNC/UAMS

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/17/2006
Publication Date: 5/2/2006
Citation: Dave, B., Eason, R.R., Geng, Y., Su, Y., Badger, T.M., Simmen, R.C. 2006. Tp53-associated growth arrest and DNA damage repair gene expression is attenuated in mammary epithelial cells of rats fed whey proteins. Journal of Nutrition. 136:1156-1160.

Interpretive Summary: Occurrence of mammary cancer can be influenced by diet. Using a rat model of mammary carcinogenesis, we previously demonstrated that dietary whey proteins can reduce the incidence of and delay mammary tumor development. In the present study, we show that dietary whey proteins can increase the health status of mammary tissues by increasing the body’s ability to produce factors with the ability to kill tumor cells. This means that rats fed diets made with whey proteins have less breast cancer and we would predict, therefore, that the same effects would occur in women. Thus, whey protein consumption may help prevent breast cancer in women. Our future studies will learn more about how this occurs and how to apply these results to women.

Technical Abstract: Dietary protection from mammary cancer is likely coordinated through multiple signaling pathways, based on the known heterogeneity of the disease and the distinct origins of mammary tumor cells. The present study examined the modulatory effects of dietary intake of whey protein hydrolysate (WPH) relative to casein (CAS), on mammary epithelial cell resistance to endogenous DNA damage using Tp53 gene expression and signaling as a read-out, and on systemic proapoptotic and immune surveillance activity, in young adult female Sprague-Dawley rats. Rats were fed AIN-93G diest made with CAS or WPH as the sole protein source beginning at gestation d 4. At postnatal day (PND) 50, mammary glands of rats fed WPH had lower levels of activated Tp53 and p38 mitogen-activated protein kinase proteins, and reduced transcript levels for Tp53-associated DNA damage repair, growth arrest, and proapoptotic genes than those of CAS-fed rats. Serum from PND50 rats fed WPH had greater apoptotic activity in MCF-7 tumor cells than from rats fed CAS, while serum from rats of either diet group did not induce apoptosis in non-tumor MCF-10A cells. Serum levels of monocyte chemotactic protein (MCP)-1 were higher in WPH- than in CAS-fed rats. MCF-7 cells treated with CAS serum + recombinant MCP-1 showed comparable apoptotic activity as well as Tp53 and p21 gene expression levels as those treated with WPH serum or recombinant MCP-1. Results indicate that mammary glands of rats fed WPH diet are more protected from endogenous and exogenous DNA damage than are those of CAS-fed rats, and identify MCP-1 as a potential serum biomarker for the positive effects of healthy diets.