Maternal blueberry diet suppresses Wnt1‐induced mammary tumor progression in offspring

Abstract

Despite the well‐accepted notion of peri‐natal origins of adult diseases, the factors and regulatory mechanisms underlying breast cancer development remain unclear. Diet is a highly modifiable determinant of breast cancer risk, and the effects of the in utero nutritional environment persist beyond fetal life. We investigated whether in utero/lactational exposure to blueberry (BB) via maternal diet alters the trajectory of Wnt1‐induced mammary tumorigenesis in offspring. Wnt1 transgenic mice were exposed to maternal diets of casein (CAS; n=33) or blueberry‐supplemented CAS (3% BB; n=28) from gestation day 4 until post‐natal day 21. Offspring were then weaned to CAS and mammary tumor development was followed until age 8 months. While tumor incidence and latency were similar for both groups, tumor weight (by 2‐fold, p=0.034) and growth rate (by 60%; p=0.008) were reduced in offspring of BB‐ versus CAS‐fed dams. Tumors from the BB group had higher expression of tumor suppressors PTEN and E‐cadherin and lower cyclin D1 and pro‐apoptotic Bcl2 levels. Transcript levels for DNA methylation enzymes DNMT1 and EZH2 were higher in BB tumors. Serum levels of insulin and serum leptin/adiponectin ratio were lower for tumor‐bearing BB than CAS offspring at sac. Our findings support a role for nutritional epigenetics in adult breast cancer outcome.Grant Funding Source : USDA‐CRIS (RCMS), DOD‐BCRP (OR) and NIH‐NCI (FAS).