Tumor Suppressor Gene Protects Against Pre-Cancerous Development
Pre-cancerous cell growth
Cell biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have provided further evidence that a gene thought to play a role in suppressing tumors actually can protect against the development of pre-cancerous cell growth as well. The researchers say that the gene, caveolin-1 (Cav-1), which they found in two major types of breast cells, could be a potential target for future drugs aimed at preventing breast cancer. The work also suggests a potentially important role of the tumor "microenvironment" in the cancerous process.
Cav-1 is involved in breast cancer onset and progression, and it's present in epithelial cells and mammary "fat pads," or stromal cells. The researchers, led by Michael Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University and Jefferson's Kimmel Cancer Center, showed striking effects in mice that lacked Cav-1, particularly in stromal cells.
Reporting November 1, 2006 in the American Journal of Pathology, Dr. Lisanti, Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College, and their co-workers showed in a series of experiments that tumor cells grew larger in mammary fat pads lacking Cav-1, and that metastatic breast cancer cells transplanted to fat pads with Cav-1 failed to grow.
"There could also be human conditions where loss of Cav-1 in the stroma could be predisposing patients toward increased risk," Dr. Lisanti says. "This provides the hard genetic evidence of a cause-effect relationship between loss of Cav-1 in the stroma and tumor growth. This could be predictive by looking at Cav-1 in the stroma and seeing if this is a bad risk factor."
The researchers found that mice lacking the Cav-1 gene showed a cell thickening in the breast duct and hyperplasia