Neonatal Experiences Differentially Influence Mammary Gland Morphology, Estrogen Receptor α Protein Levels, and Carcinogenesis in BALB/c Mice

Prevention of breast cancer can be achieved with a better understanding of the factors contributing to normal breast development. Because the breast develops postnatally, alterations in the development and lifetime activity of the neuroendocrine system may set up an environment that increases cancer risk. The present study examined how two neonatal experiences over the first 3 weeks of life influence normal and malignant mammary gland development in female BALB/c mice. Following puberty, both brief (15 minutes) and prolonged (4 hours) daily maternal separations of newborn mice accelerated mammary gland development relative to nonseparated mice. Despite similar mammary gland morphologies between mice exposed to these two neonatal separation experiences, only mice exposed to prolonged maternal separation bouts showed a higher incidence and faster onset of mammary tumorigenesis following adulthood carcinogen [7,12-dimethylbenz(a)anthracene] administration. Molecular analysis of estrogen receptor alpha (ER alpha) and p53, two proteins that have been implicated in breast cancer, revealed that for mice exposed to prolonged neonatal maternal separation bouts, mammary gland ER alpha protein levels were upregulated in a transcription-independent manner. On the other hand, p53 expression in mammary glands of adult mice was not differentially influenced by neonatal experiences. Our findings show that chronic, moderate psychosocial stress during the neonatal period increases the expression of ER alpha protein and promotes mammary tumorigenesis in adulthood. Cancer Prev Res; 3(11); 1398-408. (C) 2010 AACR.