|Rahal, Omar -|
|Pabona, John Mark -|
|Hennings, Leah -|
|Prior, Ronald -|
|Kelly, Thomas -|
|Al-Dwairi, Ahmed -|
|Simmen, Frank -|
|Simmen, Rosalia -|
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: December 15, 2011
Publication Date: April 1, 2012
Citation: Rahal, O., Pabona, J., Hennings, L., Prior, R.L., Kelly, T., Al-Dwairi, A., Simmen, F.A., Simmen, R.C. 2012. Maternal blueberry diet programs Wnt-1-induced mammary tumor progression and gene expression in mouse offspring. The Federation of American Societies for Experimental Bilogy Journal. 26 (Meeting Abstracts):128.4. Interpretive Summary: The risk of adult diseases such as breast cancer can be modified by exposure to certain environmental factors such as diet during early stages of life such as pregnancy and lactation. In the present study, we evaluated the effect of blueberry feeding during pregnancy and lactation on breast cancer in the offspring. We showed that maternal blueberry diet protects mice against breast cancer development by up-regulation of growth suppressor proteins and hormones that are associated with obesity and inflammation. Our findings provide important evidence for role of early dietary intervention to prevent adult onset of breast cancer.
Technical Abstract: Despite the well-accepted notion of peri-natal origins of adult diseases, the factors and regulatory mechanisms underlying breast cancer development at later adult life remains 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. Wnt-1 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 PTEN and E-cadherin and lower cyclin D1 and Bcl2 levels. Transcript levels for DNA methylation enzymes DNMT1 and EZH2 were also higher in BB tumors. Serum levels of insulin but not adiponectin, leptin and IGF-1, differed between tumor-bearing BB and CAS offspring at sac. Our findings support a role for nutritional epigenetics in adult breast cancer outcome.