August 13, 2012
A team of researchers at Case Western Reserve University School of Medicine, led by Dr. Mark W. Jackson, have developed a novel method to identify genes that, when overexpressed, make normal cells behave like cancer cells. Using this method, the Jackson laboratory has identified a new oncogene, which is a gene that contributes to the development of cancer, named FAM83B.
"We made our discovery in a model of breast cancer," said Mark W. Jackson, PhD, Assistant Professor, Department of Pathology, Case Western Reserve University School of Medicine, Case Comprehensive Cancer Center. "Using an unbiased screening approach, we let the biology of cancer formation tell us what genes are important and FAM83B was one of the genes that came out of our screen. When FAM83B was overproduced in normal breast cells, it transformed the normal cells, causing them to behave like breast cancer," stated Jackson.
There are relatively few oncogenes that are critical to breast cancer growth, and only one other breast cancer oncogene has been identified in the last six years. Breast cancers are classified clinically into subgroups based on the presence of specific proteins, including estrogen receptor (ER), progesterone receptor (PR), and HER2.
"Analysis of breast cancer revealed that elevated FAM83B expression is associated with the more aggressive, triple negative subgroup which lacks ER, PR and HER2," said Jackson. "In short, patients with triple-negative breast cancer would benefit most from the development of new therapeutics."
Novel oncogenes provide opportunities for drug development that may expand the number of therapies available for eradicating cancer and extending the life of patients. "Our discovery provides the foundation for developing new therapies that can inhibit FAM83B in these aggressive cancers, which have traditionally been difficult to treat. We are currently trying to identify drugs that that can inhibit the function of FAM83B, " stated Jackson.
This study will appear in The Journal of Clinical Investigation and will be co-published with a discovery from the laboratory of Dr. Mina Bissell at Lawrence Berkley National Laboratories. Dr. Bissell’s laboratory discovered an oncogene called FAM83A. Both FAM83A and FAM83B belong to an eight member family of genes that both laboratories propose may drive tumor formation and therapeutic resistance.
Dr. Jackson is the principal investigator leading a multidisciplinary team with investigators that include: Rocky Cipriano, James Graham, Kristy Miskimen, Benjamin Bryson, Ronald Bruntz, Sarah Scott, H. Alex Brown and George Stark. Additional support for the research came from the Case Comprehensive Cancer Center, the United States National Institutes of Health (R01CA138421 to M.W.J; T32CA059366 to R.C), the Department of Defense Breast Cancer Research Program (M.W.J), the American Cancer Society (RSG-10-072-01-TBG to M.W.J) and the McDonnell Foundation (to H.A.B).