Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/17/2005
Publication Date: 8/2/2005
Citation: Eason, R.R., Till, R.S., Velarde, M.C., Geng, Y., Chatman, L., Gu, L., Badger, T.M., Simmen, R.C. 2005. Uterine phenoytpe of young adult rats exposed to dietary soy or genistein during development. Journal of Nutritional Biochemistry. 55(10):625-632.
Interpretive Summary: This study shows that whey proteins, a component of human and cow milk, can be protective against development of mammary tumors in rats. These findings have important implications for nutrition of children.
Technical Abstract: We have found that AIN-93G diets made with whey protein hydrolysate (WPH) reduce DMBA-induced tumor incidence in Sprague-Dawley (Harlan) rats relative to those fed diet with casein (CAS). Herein, we replicated these findings in another Sprague-Dawley sub-strain (Charles Rivers) and examined whether WPH protective effects were associated with altered mammary gland differentiation status and expression of the tumor suppressor PTEN. Mammary tumor incidence was lower in DMBA-treated rats fed WPH than in those fed CAS. Mammary glands of WPH- and CAS-fed rats were isolated at weaning (PND 21-28) and at an early adult stage (PND50-53), and analyzed for proliferative (PCNA immunoreactivity), apoptotic (TUNEL), and differentiation ('-casein) indices, as well as for PTEN mRNA and protein levels. PND 50-53 rats fed WPH showed decreased proliferation and increased apoptosis in mammary structures, coincident with increased mammary '-casein gene expression, decreased terminal end-bud numbers, and increased ductal lengths, relative to same-aged CAS-fed rats. When challenged with DMBA for 24 h, mammary glands of PND53 CAS-fed rats had decreased cell survival in both terminal end buds and ductal epithelium, while those of WPH-fed rats were not altered from pre-DMBA levels. At 7 d post-DMBA, mammary glands of CAS- and WPH-fed rats exhibited comparable apoptotic indices. Mammary PTEN expression was higher in WPH- than in CAS-fed rats at PND21-28, but was not different in young adults fed either diet. Results demonstrate that dietary WPH advances mammary gland differentiation during neonatal development and suggest that the transiently increased expression of the pro-apoptotic signal PTEN during a sensitive developmental window may partly underlie the cancer protective effects of WPH.