title: Neonatal experiences differentially influence mammary gland morphology, estrogen receptor {α} protein levels, and carcinogenesis in BALB/c mice.
abstract: 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 α (ERα) and p53, two proteins that have been implicated in breast cancer, revealed that for mice exposed to prolonged neonatal maternal separation bouts, mammary gland ERα 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 ERα protein and promotes mammary tumorigenesis in adulthood.
authors.affiliation: Trent University, Peterborough, Ontario, Canada.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Boyd
authors.forename: Ayesha
authors.initials: A
authors.lastname: Salleh
authors.forename: Brent
authors.initials: B
authors.lastname: Humber
authors.forename: Janet
authors.initials: J
authors.lastname: Yee
authors.forename: Ladislav
authors.initials: L
authors.lastname: Tomes
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Kerr
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000523:psychology; D008426:Maternal Deprivation; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D002273:Carcinogens; D047628:Estrogen Receptor alpha; D015127:9,10-Dimethyl-1,2-benzanthracene