Pepper J. Schedin Associate Professor Medical Oncology Ph.D., Molecular, Cellular and Developmental Biology University of Colorado at Boulder University of Colorado Cancer Center Mail Stop 8117 P.O. Box 6511 Aurora, CO 80045-0511 Office Tel: 303-724-3873, Lab: 303-724-3889 Pepper.Schedin@UCHSC.edu

The long term objective of the Schedin Lab research program 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. I have proposed that the natural tissue remodeling that occurs in the mammary gland following pregnancy and lactation promotes breast cancer progression, accounting for 'the dual effect' of pregnancy. I propose that the tumor promoting activity of physiologic mammary gland regression is due to an inflammation-like microenvironment that is present during gland regression. The hypothesis that mammary stroma from an actively involuting mammary gland promotes tumor progression is being evaluated using both in vivo and in vitro model systems. ECM proteins that activate tumor cells invasion are being identified using proteomic approaches.

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 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 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

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, 28:259-266, 2006.

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, 137: 1415-1472, 2007.

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, 1415-1472, 2007.

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., Pregnancy-associated breast cancer and metastasis. Nature Reviews Cancer, 6:281-291, 2006.

Kwak HI, Gustafson T, Metz RP, Laffin B, Schedin P, Porter WW. Inhibition of breast cancer growth and invasion by single-minded 2s.
Carcinogenesis. 2006 Jul 13

Schedin, P., Strange, R., Mitrenga, T., Wolf, P., and Kaeck, M. Fibronectin fragments induce MMP-activity in mouse mammary epithelial cells; evidence for a role in tissue remodeling. J. Cell Science, 113:795-806, 2000.

Bemis, L.T., and Schedin, P. Reproductive state of rat mammary gland stroma modulates breast cancer cell migration and invasion. Cancer Research, 60: 3414-3418, 2000.

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.

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, 2004, 24(2): 1766-1779.

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.

Latest Publications in PubMed