Oncological Sciences

E-mail: david.jones@hci.utah.edu
Address: 5262 Huntsman Cancer Institute
Phone: 585-6107

APC and Retinoic Acid in Colon Cancer Development

Research description:   Colorectal cancer is the third most common malignancy in terms of new cases and deaths among men and women in the United States.   Our long-term goal is to facilitate the development of new preventive measures for colon adenoma formation by understanding the earliest cellular perturbations that follow mutations in the APC gene. The APC gene is mutated in 80% of all colon cancer cases and is thought to cause colon adenomas by promoting proliferation and preventing proper differentiation of colonocyte.   However, our understanding of how APC promotes colonocyte differentiation is limited. In this respect, we have shown that human colon adenomas and carcinomas show a profound deficiency of retinoic acid biosynthetic enzymes.   Furthermore, re-introduction of wildtype APC into an APC-deficient colon cancer cell line induced retinol dehydrogenases and increased retinoic acid production. Our observations suggest a novel model wherein APC promotes colonocyte differentiation by controlling retinoic acid biosynthesis. Projects in my lab utilize human cells and zebrafish as model systems for examining how APC controls retinoic acid production and the potential of restoring this defect by treating colon adenomas and carcinomas with retinoid derivatives.

Does this research involve human subjects or animals? Yes

If yes, what is the protocol number? IACUC 04-09005

11/2004