Tan A. Ince, MD, PhD

2009-2010 BCRF Project:
(made possible by generous support from Play For P.I.N.K.)

The normal human breast tissue has many different cell types; among these, Dr. Ince and colleagues converted two different normal human breast cell types into tumorigenic cells through the introduction of an identical set of gene mutations. The resulting tumors differed significantly despite having identical DNA mutations. The tumors created from one cell type formed tumors in models when only 10 cells were injected, and these tumors frequently spread to the lungs; in contrast, the tumors derived from another normal breast cell never spread to other organs and required injection of 1,000,000 cells to form tumors in models. Since the researchers used the same genetic mutations to induce these tumors from two different normal breast cell types from the same person, they conclude that the normal cell-of- origin plays an important role in determining the behavior of breast cancers. They have now identified twelve different normal cell types in normal human breast and think that these cells give rise to different breast tumor subtypes (ER+, HER2+, triple negative and their subtypes). In collaboration with other BCRF investigators they are now examining if tumors that arise in different cells have different clinical outcomes and different responses to the same treatment.

Mid-Year Progress Report:
Dr. Ince's previous work suggested that the normal cell-of-origin of human breast tumors may significantly influence behavior. During last grant period his team identified seven different normal human breast cell types that may serve as cell-of-origin for a tumor. During this grant period they determined that vast majority of human breast tumors are similar to one of these seven normal breast cell types. Next they will examine if these tumor types predict tumor behavior and clinical outcome.

Bio:
Dr. Ince is an Associate Professor of Pathology and director of Tumor Stem Cell Division at the Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine. After receiving his MD at Hacettepe University in Ankara, Dr. Ince received a PhD degree in Pharmacology from Cornell University. During this work, he identified a novel DNA binding site for the tumor suppressor protein p53 that regulates human multidrug resistance gene (MDR1), which may contribute to chemotherapy resistance in p53 mutated tumors. Following basic science training at Cornell, he continued his clinical training in Anatomic and Surgical Pathology at Massachusetts General Hospital and completed a subspecialty fellowship in breast and gynecologic pathology at Brigham and Women's Hospital, Harvard Medical School.

Dr. Ince received a career development award from National Cancer Institute for advanced research training in the laboratory of Dr. Robert Weinberg at the Whitehead Institute, Massachusetts Institute of Technology, where he stayed during 2000-07. While at the Whitehead Institute, Dr. Ince developed a new cell culture nutrient medium that is now widely used to grow human breast and ovary cells in the laboratory. This advancement provided the opportunity to directly compare genetically identical tumors that were created from various distinct normal human breast cell types. This work revealed that tumor cell behavior is strongly influenced by the nature of the normal cell type that serves as the precursor of the tumor cells.