Poster abstracts
Poster number 71 submitted by Clarissa Wormsbaecher
In utero BPA exposure alters the extracellular matrix to increase mammary gland density and stiffness
Clarissa Wormsbaecher (Department of Molecular Genetics, The James Comprehensive Cancer Center), Andrea R. Hindman (Department of Molecular Genetics, The James Comprehensive Cancer Center), Claire E. Kovalchin (Department of Molecular Genetics), Alex Avendano, Jonathan W. Song (Department of Mechanical and Aerospace Engineering, The James Comprehensive Cancer Center), Xingyan Kuang (Center for Biostatistics, The Wexner Medical Center), Craig J. Burd (Department of Molecular Genetics, The James Comprehensive Cancer Center)
Abstract:
In utero exposure to estrogenic endocrine disruptors increases a woman’s lifetime risk of breast cancer. Similarly, mice exposed in utero to BPA have increased susceptibility to mammary gland tumors. However, it is unclear which BPA-induced alterations predispose the mammary gland to cancer transformation in adulthood and promote tumor growth. Herein, we performed RNA-sequencing analysis on enriched mammary gland cell populations (luminal epithelial, basal epithelial/ mammary stem cell (MaSC), and fibroblast) from adult mice which had been exposed in utero to BPA or an oil control. Interestingly, the luminal epithelial cells most likely to transform to cancer showed few transcriptional alterations. However, we found a large number of genes altered in the fibroblast population. Ingenuity pathway analysis on the deregulated fibroblast genes identified the extracellular matrix as the most altered cellular component and we identified significant deregulation of collagen genes. In fact, BPA exposed mammary glands displayed increased collagen in the mammary gland. Using a novel in vitro fluidics system, we demonstrate that primary fibroblasts from BPA exposed mice remodel collagen and decrease fluid permeability of the extracellular matrix, which is indicative of an increased density in the extracellular matrix. We also found that mammary glands exposed to BPA in utero are more stiff, using an in vivo testing method. As changes to breast density, stiffness, and collagen deposition are all associated with breast cancer risk, these data indicate that one target of BPA action is through stromal remodeling of the mammary gland to increase susceptibility to breast cancer.
Keywords: BPA, breast cancer , endocrine disruptors