Tan A. Ince, M.D., Ph.D.
Associate Professor of Pathology
Description of Research
Dr. Ince's research focuses on the role of cell-of-origin in determining tumor phenotype and development of culture systems for in vitro culture of primary human tissues and tumors.
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 (BPECs) exhibited the typical features of tumor stem cells (TSC) and formed tumors in mice when only 10 cells were injected. These cells formed adenocarcinoma-like tumors in mice associated with desmoplastic reaction similar to human breast tumors, and frequently metastasized to the lungs. In contrast, the tumors derived from another normal breast cell type (HMECs) formed squamous carcinomas with no desmoplastic reaction, never spread to other organs and required injection of 100,000 cells to form tumors in mice. Since these cells were ostensibly isogenic, Ince and colleagues concluded that the phenotypic differences of these tumors, including the dramatic difference in the frequency of TSC-like cells result from epigenetic differences between their different normal cell origins. The follow up studies that expand on this initial work are designed to describe the histone modification and DNA methylation patterns that are associated with tumor phenotypes and tumor stem cells.
Additional areas of investigation in this laboratory are examination of heat shock protein (HSP) influence on ovarian and breast tumor stem cell phenotype, development of genetically engineered human malignant mesothelioma and ovarian carcinoma models, analysis of cell origin influence on the phenotype of induced pluripotent stem cells (iPS), and development of culture systems for carcinoid tumors, adenoid cystic carcinoma, ovarian and breast carcinomas.
- Dr. Ince invented a chemically-defined serum-free culture medium that is widely used by many investigators to grow normal primary human breast cells and their transformed derivatives in culture.
- Demonstration of the influence of cell origin on breast tumor phenoptype
- dentification of a non-canonical repressor DNA binding site for p53 protein Development of an in vitro transcription system
Selected Cancer-Related Publications
- Lin MC, Lomo L, Baak JP, Eng C, Ince TA, Crum CP, Mutter GL. Squamous morules are functionally inert elements of premalignant endometrial neoplasia. Mod Pathol 22(2):167-74, 2009 Read more »
- Elmasri H, Karaaslan C, Teper Y, Ghelfi E, Weng M, Ince TA, Kozakewich H, Bischoff J, Cataltepe S. Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells. FASEB J 23(11):3865-73, 2009 Read more »
- Jarboe EA, Folkins AK, Drapkin R, Ince TA, Agoston ES, Crum CP. Tubal and ovarian pathways to pelvic epithelial cancer: a pathological perspective. Histopathology 55(5):619, 2009 Read more »
- Chan EM, Ratanasirintrawoot S, Park IH, Manos PD, Loh YH, Huo H, Miller JD, Hartung O, Rho J, Ince TA, Daley GQ, Schlaeger TM. Live cell imaging distinguishes bona fide human iPS cells from partially reprogrammed cells. Nat Biotechnol 27(11):1033-7, 2009 Read more »
Collaborating in the Multidisciplinary Research Program(s):