Although previous research has suggested that a section of chromosome 16 harbors a tumor suppressor gene in several types of human cancers, the particular gene responsible has not previously been identified. By studying the genes within the section of chromosome 16, the Emory scientists found that ATBF1 was a strong candidate for an important tumor suppressor gene because its function is frequently lost in prostate cancer through gene mutations and/or loss of expression. In addition, ATBF1 was found to inhibit cell growth in culture dishes. A tumor suppressor gene is a gene whose loss of function contributes to the development of cancer.
ATBF1 is a transcription factor (regulator of gene expression) that functions to regulate the expression of other genes. If its function is impaired by mutations or loss of expression, a cell could lose the control of cancer genes. The Myb oncogene, for example, is normally inhibited by ATBF1, but it can be activated if ATBF1 is lost.
"Sporadic cancers often are the result of multiple genetic alterations that accumulate over time," said Dr. Dong, "but only a small number of genes have been shown to undergo these frequent mutations. Because ATBF1 inhibits cell proliferation, frequent acquired mutations that inhibit the gene, such as the ones we found, could lead to a lack of growth control in prostate cancer. Because gene deletion in chromosome 16 is common in many types of cancer, including lung, head and neck, nasopharynx, stomach, breast, and ovary, ATBF1 could be involved in the development of these cancers as well."
The research was supported by grants from the National Cancer Institute, the Department of Defense Prostate Cancer Research Program and the Georgia Cancer Coalition.
Nature Genetics