The intestine is a complex and dynamic organ that, under normal physiologic conditions, performs a number of functions in the organism, some of which, including nutrient absorption, are essential for survival. The intestine is subject to pathologic disturbances in a number of diseases affecting humans, including developmental malformations, inflammatory bowel disease (affecting 1 million people in the US each year), and cancer, including colon cancer (which accounts for 10% of cases of cancer and 10% of deaths from cancer in men and women each in the US each year). Members of the Ets transcription factor family are important regulators of pathways that mediate cell growth, differentiation, and interactions between cells and the surrounding environment. There is evidence that Ets factors are important in the formation and normal function of the intestine, in intestinal injury, such as occurs in inflammatory bowel disease, and in intestinal (colon) cancer. The long-term objectives of the proposed studies are to elucidate how Ets factors impact these processes. We have developed an animal (mouse) model system designed to block or enhance Ets factor function in the developing and adult intestine in the living organism. We now propose to use this model system to characterize how Ets factors regulate the formation and maintenance of the functional unit of the intestine (the so-called """"""""crypt-villus axis"""""""") under normal conditions and conditions of intestinal injury, as well as how they regulate the initiation and/or progression of intestinal (colon) cancer. As the studies will be conducted in a mouse model system, in which intestinal structure and function are extremely similar to those in humans, it is expected that the information learned will have direct relevance to the understanding of normal intestinal function and disease, including inflammatory bowel disease and colon cancer, both prevalent diseases causing significant suffering and death, in humans.
| Kern, Hanna B; Niemeyer, Brian F; Parrish, Janet K et al. (2012) Control of MicroRNA-21 expression in colorectal cancer cells by oncogenic epidermal growth factor/Ras signaling and Ets transcription factors. DNA Cell Biol 31:1403-11 |
| Jedlicka, Paul; Sui, Xiaomei; Gutierrez-Hartmann, Arthur (2009) The Ets dominant repressor En/Erm enhances intestinal epithelial tumorigenesis in ApcMin mice. BMC Cancer 9:197 |
| Jedlicka, Paul; Sui, Xiaomei; Sussel, Lori et al. (2009) Ets transcription factors control epithelial maturation and transit and crypt-villus morphogenesis in the mammalian intestine. Am J Pathol 174:1280-90 |
| Jedlicka, Paul; Gutierrez-Hartmann, Arthur (2008) Ets transcription factors in intestinal morphogenesis, homeostasis and disease. Histol Histopathol 23:1417-24 |
