Tan A. Ince, MD, PhD

Our project on normal breast cell types took nearly 10 years to produce results. Such long-term project is not possible to fund through conventional funding mechanisms with much shorter timeline and incremental vision. We examined nearly 15,000 normal cells and almost 3,000 tumors, which was only possible through BCRF/PFP funding.

Scientific Director, Live Tumor Culture Core and Tissue Bank Core Facility
Director, Tumor Stem Cell Division, Interdisciplinary Stem Cell Institute
Associate Professor, Department of Pathology
University of Miami
Miami, Florida

2016-2017 PROJECT

Many environmental and lifestyle factors including diet, exercise, and hormones influence development of breast cancer. These effects are not easily explained by genetics because hormonal and environmental factors do not cause genetic mutations outright. However, they may affect how DNA is packaged in cells and thus which genes are “turned on” or “turned off.”

Dr. Ince’s research has shown that DNA packaging occurs differently in different cells and that a cell’s “epigenetic program” (chemical modification of the DNA) can determine if the cell becomes cancerous, including its ability to metastasize (spread to other tissues).

His laboratory has identified 10 breast cell types with distinct epigenetic programs and combinations of hormone receptors that give rise to cancers with significant differences in behavior and response to treatment. They discovered that estrogen receptors, androgen receptors, and vitamin D receptors work with DNA packaging proteins to regulate cancer stem cells. This observation may explain environmental influences on breast cancer that cannot be explained by DNA mutations.

The goal of Dr. Ince’s research is to translate these discoveries to the clinic and develop new strategies for treatment, because unlike genetic mutations that are permanent, epigenetic changes are reversible.

BIO

Dr. Ince received his PhD in Pharmacology from Cornell and completed clinical training at Massachusetts General Hospital, Brigham and Women’s Hospital, and Harvard Medical School. Dr. Ince was a visiting clinical scientist at Massachusetts Institute of Technology, 2000-2007, where he developed a new cell culture nutrient medium that is now widely used to grow human breast and ovary cells. In 2010, he was recruited to the Braman Family Breast Cancer Institute at the University of Miami Miller School of Medicine.

Dr. Ince’s research focuses on the role of normal cell-of-origin in determining tumor phenotype and development of culture systems for in vitro culture of primary human tissues and tumors. The use of normal cell types as a reference to classify tumors, however, has not been widely emulated in solid tumors, partly due to a more limited understanding of epithelial cell differentiation. Dr. Ince used a new and innovative multiplexed immunofluorescence technology to monitor multiple markers simultaneously in the very same cells. Based on the study Dr. Ince and colleagues described eleven new normal breast subtypes and showed that each human tumor is similar to one of these normal cell types. These results led to new normal cell type based classification of breast cancers that has important implications for understanding breast cancer prognostics and how breast cancer is treated. In brief, the results of this study indicate that breast tumors arising from different normal cells have significantly different clinical outcomes and drug response, and should be classified and treated differently.