The effect of alcohol exposure during post-lactational involution on mouse mammary tumorigenesis
Marthappa Shenoy, Rajani
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Breast cancer susceptibility is influenced by dynamic stromal remodeling of the mammary tissue during its various stages of development, such as puberty, pregnancy, lactation, and post-lactational involution. Epidemiological studies suggest that parity reduces a woman's lifetime risk of developing breast cancer. But this protective effect of pregnancy is neither immediate nor constant; recent studies have shown that the developmental window of post-lactational involution significantly increases the risk of parity associated breast cancer. The period of involution has been recognized as a sensitive time point when the mammary tissue may be highly susceptible to carcinogens. The purpose of this study was to test the hypothesis that ethanol, a known carcinogen for breast cancer, enhances tumorigenesis when administered during post-lactational involution. FVB-MMTV-Her2/Neu transgenic mice, which spontaneously develop mammary tumors, were fed isocaloric liquid diets containing 0, 0.5%, 1%, or 2% ethanol for 14 days. This feeding occurred during involution initiated after 21 days of lactation. Serial tracking of tumors by palpation showed that ethanol had no effect on latency, multiplicity, or growth rate of primary tumors. A significant increase in the total tumor burden was observed only between the 0 and 0.5% ethanol dietary groups (p-value of 0.006). Histopathology of primary tumors was unchanged by diet in terms of nuclear score, glandular differentiation or mitotic index. Metastases to lungs were also unaffected by ethanol. qRT-PCR analyses of RNA isolated from primary tumors showed no significant change in expression of ErbB2, aromatase, COX-2, and TGF-beta, which we predicted would be susceptible to modification by ethanol. These results suggest that the mature mammary gland is refractory to the effects of ethanol during involution following extended (21 days) lactation. Future studies will compare the effects of ethanol exposure during acute involution initiated during peak lactation.