Tp53-Associated Growth Arrest and DNA Damage Repair Gene Expression Is Attenuated in Mammary Epithelial Cells of Rats Fed Whey Proteins

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 diets 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 WPH-fed rats had greater apoptotic activity in MCF-7 tumor cells than that from rats fed CAS. Serum levels of monocyte chemoattractant protein (MCP)-1 were higher in WPH- than in CAS-fed rats. MCF-7 cells treated with CAS serum + recombinant rat MCP-1 had apoptotic activity and Tp53 and p21 gene expression levels comparable to those treated with WPH serum or recombinant MCP-1. Results indicate that mammary glands of rats fed a WPH diet are more protected from endogenous 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.