"For a long time, scientists believed they knew what the APC gene did that it regulated cell growth and division but now we know we've been missing a big piece of the picture," reports David Jones, Ph.D., principal investigator of the study and leader of HCI's Colon Cancer Scientific Program. "What we didn't know was that it converts vitamin A into retinoic acid, which is vital for normal colon cell development."
Jones' lab had recently demonstrated that lack of retinoic acid, induced by mutating the APC gene, led to cancerous tumors in human colon cell lines. The new study blocked APC function in zebrafish and demonstrated that when the APC gene was blocked, the fish embryos lacked normal intestinal lining cells. When the embryos were treated with retinoic acid, normal cell development was restored. Because zebrafish and humans share many genes, including the APC gene, researchers often use the little black-and-white striped fish as models to study various aspects of human development.
"Implications of this study are far reaching," Jones says. "We have long suspected that vitamin A was helpful in preventing certain cancers, including colon cancer. With this new understanding, it may be possible to bypass a non-functioning APC gene by introducing retinoids as a form of chemoprevention, and thus control the undifferentiated and uncontrolled growth of colon cells that results in colon cancer."
Several years ago, University of Utah researchers identified the APC gene, as well as an inherited colon ca