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Obesity and perinatal TCDD exposure increases mammary tumor incidence in FVB mice
Citation:
LaMerrill, M. A., R. Harper, L. S. BIRNBAUM, R. D. Cardiff, AND D. THREADGILL. Obesity and perinatal TCDD exposure increases mammary tumor incidence in FVB mice. Presented at Keystone Symposium, Taos, NM, February 19 - 24, 2008.
Impact/Purpose:
Obesity is a key risk factor for breast cancer. Animal studies have shown that both diet and TDCC can increase breast cancer risk. The purpose of this study was to determine if TCDD would enhance the effect of a high fat diet in a mouse model of breast cancer. The answer is "yes."
Description:
Breast cancer risk consistently correlates with total lifetime exposure to estrogens. Because both TCDD and adipocytes impact the estrogen pathway, we examined how TCDD and obesity interact to alter mammary cancer susceptibility. At 12.5 days post conception, we exposed FVB females to 1 µg/kg of TCDD or vehicle. To model diet-induced obesity, the nursing dams were put on high or low fat diet at birth. Female offspring were kept on the same diets after weaning exposed to DMBA at post-natal days (PND) 35, 49, and 53, and monitored for tumor development. A second FVB cohort was treated identically up until PND 50, when mammary gland mRNA was analyzed by microarrays and real time PCR. TCDD and HFD appeared to synergistically increase mammary tumor prevalence. ERα mRNA was higher in mammary tumors than in mammary tissue. Maternal TCDD exposure increased ERα mRNA in both mammary tissue and tumors compared to vehicle. High fat diet increased mammary gland metabolism, and genes involved in cancer. In summary, obesity increases the sensitivity of FVB to DMBA-induced mammary carcinogenesis. Perinatal TCDD exposure interacts with HFD to increase mammary cancer incidence, possibly through upregulation of ERα.