Two proteins that act in opposing directions one that promotes cancer and one that suppresses cancer regulate the same set of genes in prostate cancer, Vanderbilt-Ingram Cancer Center researchers have found.
The findings, reported recently in the Journal of Clinical Investigation, point toward potential drug targets and prognostic markers for prostate cancer.
"We are trying to understand the molecular genetics of prostate cancer: what are the genes that are altered in human prostate cancer, and very importantly, how do they lead to cancer when they are changed?" said Sarki Abdulkadir, M.D., Ph.D., associate professor of Pathology, Microbiology and Immunology and of Cancer Biology.
Abdulkadir's lab uses mouse models to probe the molecular pathways involved in prostate cancer.
Two separate projects in the lab unexpectedly came together for this study one led by postdoctoral fellow Philip Anderson, Ph.D., and the other spearheaded by (then) graduate student Sydika McKissic, Ph.D.
Anderson was using genomic approaches to understand how loss of a tumor suppressor protein, called NKX3.1, promotes prostate cancer. NKX3.1 is a transcription factor, meaning that it binds to and regulates the expression of other genes, turning them "on" or "off."
"It is one of the genes most commonly deleted in human prostate cancerand is lost very early," explained Abdulkadir.
Anderson isolated the NKX3.1 protein and identified a set of 9,817 genes that bind to the protein. Of that set, he identified 282 genes that are regulated by the protein i.e., their expression was altered by loss of NKX3.1.
"So we took those genes...and asked 'what is interesting about these genes?'" said Abdulkadir.
Using bioinformatics tools, the investigators found a quarter of the NKX3.1-regulated genes are also bound by a "famous" oncogene called Myc (which, like NKX3.1, is also a transcription factor).
|Contact: Craig Boerner |
Vanderbilt University Medical Center