Linda Schuler
Department of Comparative Biosciences
Office: 4354B
Education
- BS 1974, University of Wisconsin
- PhD 1980, University of Pennsylvania
- VMD 1981, University of Pennsylvania
Research
Breast Cancer
The physiologic growth, differentiation and functional activity of the breast are orchestrated by a network of hormones, growth factors, and developmental regulators. Not surprisingly, many of these same factors have been found to play critically important roles in the development and progression of breast cancer. Understanding this interplay can lead to effective specific therapeutic approaches, minimizing side effects to patients, as well as potential preventative strategies.
Transcript profiling has enabled division of breast cancers into subtypes that may have different etiologies and may be susceptible to specifically targeted therapies. So-called "luminal" breast cancers [those that express estrogen receptor alpha (ERa+)] comprise about 75% of breast tumors. Although therapies directed at ERa are quite effective for this subtype, these regimens fail in about 25% of patients, who either are initially resistant or later develop resistance. Thus, understanding the pathogenesis and progression of luminal breast cancer would save the lives of many women.Prolactin is a principle regulator of mammary epithelial proliferation and differentiation, consistent with a key role in breast cancer. Recent epidemiologic studies support its importance in "luminal" tumors. Elevated circulating prolactin is associated with a higher risk for development of this type of tumor, established tumors express higher levels of prolactin receptors than adjacent normal tissue, and evidence for prolactin activity is associated with disease progression and resistance to endocrine and conventional chemotherapies.In order to understand the mechanisms whereby prolactin contributes to breast cancer, we have developed unique systems. Our transgenic mouse model, NRL-PRL, is one of the very few mouse models of clinical luminal breast cancer. This model enables us to examine the effects of prolactin on mammary stem and progenitor cells, as well as cancer stem cells. In conjunction with other transgenic and knockout models, we can examine crosstalk with identified oncogenic factors in the dynamic in vivo physiologic context. Our cell culture models facilitate molecular dissection of implicated signaling pathways, roles of cell context, including extracellular matrix, and mechanisms of interactions with other hormones and growth factors, including receptor trafficking.These studies have implications not only for carcinogenic processes leading to breast cancer, but also for development of prostatic cancer, which shares many underlying processes.
Responsibilities
Professor
Graduate Training
Graduate training and other affiliations
- Cellular and Molecular Biology
- Molecular and Environmental Toxicology
- Endocrinology/ Reproductive Physiology
- Comparative Biomedical Sciences Graduate Program
- MD/ PhD
- Biotechnology
- Cancer Biology
- Molecular and Cellular Pharmacology
- Department of Medicine, affiliate faculty
- Center of Women's Health and Women's Health Research
- Comprehensive Cancer Center
Recent Publications
Arendt, L.M., D.E. Rugowski, T.A. Grafwallner-Huseth, M.J. Garcia-Barchino, H. Rui and L.A. Schuler. Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer, Breast Cancer Research 13:R11, 2011. PMCID: 2665765
Carver, K.C., L.M. Arendt and L.A. Schuler. Complex prolactin crosstalk in breast cancer: new therapeutic implications. Mol. Cell. Endocrinol. 307:1-7, 2009. PMCID: 3190192
Arendt, L.M., T.L. Grafwallner-Huseth and L.A. Schuler. Prolactin and growth factor crosstalk reduces mammary estrogen responsiveness despite elevated ERα expression. Am. J. Pathol. 174:1065-1074, 2009. PMCID: 2665765