Date of Award
Bachelor of Science
Donald G. Matthews
Breast cancer is a prominent and lethal disease that currently affects close to three million people in the United States. Each year displays close to 250,000 new cases of breast cancer and around 40,000 deaths in the United States alone. A geographic pattern of breast cancer suggests a higher incidence in more temperate regions. Research has suggested that low Vitamin D levels associated with reduced sun exposure might contribute to increased breast cancer incidence. In recent studies, Vitamin D has been shown to slow the proliferation of breast cancer cells, but the mechanisms involved in vivo are poorly defined. It is known that adipose tissue is involved in the progression of breast cancer. Adipose cells in the mammary tissue are not just for support, they also release signals to the epithelium known as ‘cross talk’. To shed light onto the effects of low vitamin D on adipose signaling in the mammary gland, we studied mice with adiposespecific vitamin D receptor (VDR) deletion. The goal of this project was to study the impact of VDR deletion in adipocytes on mammary gland morphology using histological and whole mount techniques. Tissues of mice with adipose specific VDR deletion (CVF strain) were compared to those of control mice (CN1 strain). By PCR we confirmed that VDR expression was reduced approximately 80% in adipose tissue of CVF mice compared to CN1 mice. Hematoxylin and Eosin Y staining for the mammary gland revealed a slight increase in the number of epithelial ducts in the CVF mice. Further quantitation of the epithelial content of the mammary glands confirmed that glands from CVF mice had higher epithelial tissue density than glands from CN1 mice. Whole mount analysis revealed significantly increased epithelial branching in the mammary glands of the CVF compared to CN1 mice. Collectively, our data indicates that deletion of VDR in adipose tissue results in increased growth of the mammary epithelial tissue. The results imply that VDR activity in the adipose compartment of the mammary gland contributes to the anti-proliferative actions of vitamin D in this tissue.
D'Angelo, Joseph, "Phenotypic Characterization of Adipose-Specific VDR Knockout Mice" (2016). Biological Sciences. 33.