Evaluation of early post-natal pig mammary gland development and human breast cancer gene expression.

Breast cancer is the second leading cause of death in women after lung cancer, and only 5% of patients with metastatic breast cancer survive beyond ten years of diagnosis. Considering the heterogeneous subclasses of breast cancer, current cancer models have shortfalls due to copy number variants, and genetic differences of humans and immunocompromised animal models. Preclinical studies indicate stem cell activity in early post-natal mammary development may be reactivated in the human adult as a trigger to initiate cell proliferation leading to breast cancer. The goal of the work reported herein was to compare genetic expression of early development, post-natal pig mammary glands to the literature reported genes implicated in different subclasses of human breast cancer. Differentially expressed genes associated with breast cancer and present in early developing pig samples include NUCB2, ANGPTL4 and ACE. Histological staining confirmed E-cadherin, Vimentin, N-cadherin, and Claudin-1, which are all implicated in malignant cancer. Due to the homology of gene expression patterns in the developing pig mammary gland and reported genes in human breast cancer profiles, this research is worthy of further study to address a potential model using mammary development cues to unravel breast cancer biology.

Methodology to analyze gene expression patterns of early mammary development in pig models.

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.