A model of gene-environment raction reveals altered mammary gland gene expression and inased tumor growth following social isolation
- Liu tum Ch Boyd
- Do Published OnlineFirst November
wnloade ention of breast cancer can be achieved with a better understanding of the factors contributing to l breast development. Because the breast develops postnatally, alterations in the development and e activity of the neuroendocrine system may set up an environment that increases cancer risk. The t study examined how two neonatal experiences over the first 3 weeks of life influence normal alignant mammary gland development in female BALB/c mice. Following puberty, both brief inutes) and prolonged (4 hours) daily maternal separations of newborn mice accelerated mammary development relative to nonseparated mice. Despite similar mammary gland morphologies en mice exposed to these two neonatal separation experiences, only mice exposed to prolonged nal separation bouts showed a higher incidence and faster onset of mammary tumorigenesis folg adulthood carcinogen [7,12-dimethylbenz(a)anthracene] administration. Molecular analysis of en receptor α (ERα) and p53, two proteins that have been implicated in breast cancer, revealed that ice exposed to prolonged neonatal maternal separation bouts, mammary gland ERα protein levels pregulated in a transcription-independent manner. On the other hand, p53 expression in mammads 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 ERα protein and promotes mammary tumorigenesis in adulthood. Cancer Prev Res; 3(11); 1398–408. ©2010 AACR.