Abstract
In mammary gland development, normal stem cell activity occurs in the embryonic stage and postnatally. Research supports that certain breast cancers contain a small sub-population of cells that mimic stem-like activity. It is believed stem cell activation in the mutated mature human mammary tissue is what drives quiescent epithelial cells to convert to mesenchymal states initiating migration, invasion, and metastasis in breast cancer. The goal of the work reported herein was to investigate early mammary development gene expression in the postnatal pig using fine needle biopsy methods in order to establish a reliable model for human breast cancer detection. Tissue samples were collected from pig mammary glands beginning at Day 11 of age through Day 39 in order to capture early postnatal-growth gene expression. Based on the initial clustering analysis, two distinct clusters of gene expression profiles occurred before and after Day 25 of mammary development. Gene set enrichment analysis (GSEA) ontology indicated the cellular processes that changed after Day 25, and many of these processes were implicated in epithelial–mesenchymal transition (EMT) signaling events. Gene expression in the postnatal pig was compared with the Epithelial–Mesenchymal Transition gene database (dbEMT) confirming the presence of EMT activity in this early developmental program. Information from this study will provide insight into early postnatal mammary gland development. In addition, mechanisms exploited by mutated mammary epithelial cells leading to cancer initiation and growth may be detected considering that mutated mammary epithelial cells can reactivate early developmental signals.
Highlights
Due to ethical considerations and minimal tissue acquisition from young human mammary glands, our current knowledge of human breast development has been limited
A change in morphology occurs after 25 days of pig mammary gland development
Tissue was collected using the Dunn Biopsy fine needle methodology which allows for genetic expression comparisons from the same animal’s tissues at different time points (Fig. 1a). This methodology removes many of the confounding effects that can be caused by collecting tissue from different animals to perform developmental analyses over time
Summary
Due to ethical considerations and minimal tissue acquisition from young human mammary glands, our current knowledge of human breast development has been limited. Interpretation of developing human breast morphology is based on analogies in the mouse. Cancer research progress has been hampered by lack of anatomically and physiologically relevant animal models, because large animal models more closely recapitulate human cancer and diseases [1]. Transitional animal models could bridge the gap between diagnostic discoveries and human clinical trials. The pig is currently advancing as a transitional model bridging the gap from mouse studies to human trials. Comparing the morphology of developing mammary glands, humans and pigs develop terminal ductal lobular units (TDLU) and epithelial proliferation is concentrated in the endbuds or TDLU’s. The mouse morphology has sparse ducts and alveolar tissue and epithelial proliferation occurs in ductal endbuds and alveoli [2]
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