Submitted to: Journal of Nutrition
Publication Type: Peer reviewed journal
Publication Acceptance Date: 9/27/2004
Publication Date: 12/10/2004
Citation: Eason, R.R., Velarde, M.C., Chatman, L., Till, R.S., Geng, Y., Ferguson, M., Badger, T.M., Simmen, R.C. 2004. Dietary exposure to whey proteins alters rat mammary gland proliferation, apoptosis, and gene expression during postnatal development. Journal of Nutrition. 134(12): 3370-3377. Interpretive Summary: Exposure of specific dietary factors early in life can help prevent, delay the onset or reduce the severity of diseases that occur later in life. In this study, we focused on the period of time around weaning in the rat (which is probably analogous to early childhood in humans). We found that a form of the minor milk proteins used throughout the world in food products is capable of advancing maturation of the breast and turning on a gene (PTEN) during a sensitive window of development. The combination of these effects is to reduce breast cancer incidence. Future studies will more carefully characterize these effects to learn better how to apply this to humans.
Technical Abstract: We have found that AIN-93G diets made with whey protein hydrolysate (WPH) refuce 7, 12-dimethyl-benz[a]anthracene (DMBA)-induced tumor incidence in Sprague-Dawley (Harlan) rats relative to those fed a 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 (Beta-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 Beta-casein gene expression, decreased terminal end-bud numbers, and increased ductal lenghts, 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 highter in WPH- than 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 suggests 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.