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Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density

By Grace Chew, Cecilia Huo, David Huang, P. Hill, Jennifer Cawson, Helen Frazer, John Hopper, Izhak Haviv, Michael Henderson, Kara Britt and Rik Thompson

Abstract

Mammographic density (MD) adjusted for age and body mass index is one of the strongest known risk factors for breast cancer. Given the high attributable risk of MD for breast cancer, chemoprevention with a safe and available agent that reduces MD and breast cancer risk would be beneficial. Cox-2 has been implicated in MD-related breast cancer risk, and was increased in stromal cells in high MD tissues in one study. Our study assessed differential Cox-2 expression in epithelial and stromal cells in paired samples of high and low MD human breast tissue, and in a validated xenograft biochamber model of MD. We also examined the effects of endocrine treatment upon Cox-2 expression in high and low MD tissues in the MD xenograft model. Paired high and low MD human breast tissue samples were immunostained for Cox-2, then assessed for differential expression and staining intensity in epithelial and stromal cells. High and low MD human breast tissues were separately maintained in biochambers in mice treated with Tamoxifen, oestrogen or placebo implants, then assessed for percentage Cox-2 staining in epithelial and stromal cells. Percentage Cox-2 staining was greater for both epithelial (p = 0.01) and stromal cells (p < 0.0001) of high compared with low MD breast tissues. In high MD biochamber tissues, percentage Cox-2 staining was greater in stromal cells of oestrogen-treated versus placebo-treated tissues (p = 0.05)

Topics: Animal, Animals, Article, Breast Neoplasms, Breast cancer, Breast density, Cox-2, Disease Models, Epithelial cells, Heterografts, Human, Humans, Mammary Glands, Mammographic density, Mice, Stroma, Stromal Cells, adult, animal, animal experiment, animal tissue, breast, breast tumor, congenital malformation, controlled study, cyclooxygenase 2, disease model, epithelium cell, estrogen, female, gene expression, genetics, human, human tissue, immunohistochemistry, mammary gland, mastectomy, metabolism, middle aged, mouse, nonhuman, pathology, priority journal, prophylactic surgical procedure, protein expression, stroma cell, tamoxifen, xenograft
Publisher: 'Springer Science and Business Media LLC'
Year: 2015
DOI identifier: 10.1007/s10549-015-3520-2
OAI identifier: oai:eprints.qut.edu.au:97703
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