The Schuler Laboratory
Faculty > Linda A. Schuler
Linda A. Schuler
Professor, Comparative Biosciences
schulerl@svm.vetmed.wisc.edu
Organ System/Disease Focus
Mammary gland/ breast cancer
Aligned Research Focus
Hormonal regulation of mammary stem and progenitor populations, and cancer stem cells
Research Description
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 factors are implicated in the development and progression of breast cancer. Understanding this interplay can lead to effective therapeutic approaches with minimal side effects, as well as potential preventative strategies.
Prolactin is a principle regulator of mammary function. Epidemiologic studies support its importance in the “luminal” subtype of breast cancer. Elevated prolactin is associated with a higher risk for this cancer, established tumors express higher levels of prolactin receptors than adjacent normal tissue, and prolactin activity is associated with disease progression and resistance to endocrine and conventional chemotherapies.
We have developed unique models to understand the underlying mechanisms. Our transgenic mouse model, NRL-PRL, enables us to examine effects on mammary stem and progenitor cells as well as cancer stem cells, and crosstalk with other oncogenic factors in the dynamic in vivo context. Our cell culture models facilitate molecular dissection of signaling pathways, 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 in breast cancer, but also for prostatic cancer, which shares many underlying processes.
Selected References
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: 3109579
Carver, K.C., T.M. Piazza and L.A. Schuler. Prolactin enhances IGF-IR phosphorylation by decreasing its association with the tyrosine phosphatase SHP-2 in MCF-7 breast cancer cells. J. Biol. Chem. 285:8003-8012, 2010. PMCID: 2832951
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
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