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Research Statement
The long term objective of the Schedin Lab is to develop breast cancer chemopreventive strategies that are targeted to specific windows of breast development. By understanding normal mammary gland development and homeostasis, it should possible to identify both mammary specific and life cycle specific chemopreventive strategies. The focus of my lab is on characterizing extracellular matrix (ECM) proteins that mediate mammary epithelial cell death during key windows of normal mammary gland differentiation, such as adolescent mammary gland development, the estrous cycle, and the pregnancy/lactation/involution cycle. Major areas of investigation include adolescent mammary development, mammary epithelial cell-stromal interactions, tissue remodeling, mammary carcinogenesis, and chemoprevention in rodent models. Current Research Projects Include: Determine the mechanism of pregnancy-associated breast cancer. Women who are diagnosed with breast cancer shortly after pregnancy have significantly reduced survival rates. We are investigating the hypothesis that the natural tissue remodeling that occurs in the mammary gland following pregnancy and lactation promotes breast cancer progression, accounting for high metastatic rate of pregnancy-associated breast cancer. This hypothesis, that the mammary microenvironment becomes pro-oncogenic during involution, is being evaluated using both 3-dimentional culture models and xenograft models for breast cancer metastasis. ECM proteins that activate tumor cells invasion are being identified using proteomic approaches. Key ECM proteins under investigation include TGFβ, MMP-9, MMP-2, and fibronectin. Identify the ECM proteomes of the ‘breast-cancer protected’ and ‘at-risk’ mammary gland. For these studies, we are isolating mammary ECM proteins from mammary glands of female rats at reduced risk of developing breast cancer either due to tamoxifen treatment or parity, and from control, ‘at-risk’ rats. The ECM proteins will be identified by proteomics and proteins in common to the ‘protected-glands’, but absent or reduced in the ‘at-risk’ glands, will be candidates for ECM proteins that mediate protection. The isolated mammary matrices are being characterized in both in vitro and in vivo models for breast cancer metastasis. The identification of dietary interventions that result in the development of mammary tissue that is resistant to carcinogenic insult. To this end, we are currently evaluating how vitamin A modifies adolescent mammary development, mammotrophic hormone signaling, and subsequent risk for carcinogenesis. Selected Publications
Schedin, P., O’Brien, J., Rudolf, M., Stein, T., and V. Borges, The Microenvironment of the Involuting Mammary Gland Mediates Mammary Cancer Progression. Journal of Mammary gland Biology and Neoplasia, Jan;12(1):71-82, 2007. McDaniel, S.M., C. O'Neill, Metz ,R., Kaeck, M., Sapuntzakis, M., Heimendinger, J, Wolfe P., Thompson, H., and Schedin, P.A comparison of whole food sources of vitamin A to retinyl palmitate on sexual maturation, mammary gland development and mammary carcinogenesis in the rat. J. Nutrition, Jan;137(6):1415-1422, 2007. Hyeong-II, K., Gustafson, T., Metz, P., Laffin B., Schedin, P., and Porter, W. Inhibition of breast cancer growth and invasion by Single-minded 2s, Carcinogenesis, 28(2):259-66, 2007. Schedin, P., Pregnancy-associated breast cancer and metastasis. Nature Reviews Cancer, 6:281-291, 2006. McDaniel, S., Rumer, K., Biroc, S., Metz, R., Singh, M., Porter, W., and Schedin, P. Remodeling of the mammary microenvironment following lactation promotes breast tumor cell metastasis. American Journal of Pathology, 168 2):608-620, 2006 Schedin, P., Mitrenga, T., McDaniel, S., and Kaeck, M. Mammary ECM composition and function are altered by reproductive state. Molecular Carcinogenesis, 41:207-220, 2004. Schedin, P. and Elias A. Multistep Tumorigenesis and the Microenvironment, Breast Cancer Research, 6: 93-101, 2004. Schedin, P., Eckel, K.L., McDaniel, S.M., Prescott, J.D., Brodsky, K.S., Tentler, J.J., and Gutierrez-Hartmann, A. ESX Induces Transformation and Epithelial to Mesenchymal Transition in MCF-12A Mammary Epithelial Cells, Oncogene, 24(2): 1766-1779, 2004. Metz, R., Kaeck, M., Stacewicz-Sapuntzakis, M., Mitrenga, T, McCarty, H., and Schedin, P. Adolescent vitamin A intake alters susceptibility to mammary carcinogenesis in the Sprague-Dawley rat. Nutrition & Cancer, 41: 78-90, 2002. |
Faculty
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