HOUSTON A single tumor-suppressing gene is a key to understanding, and perhaps killing, dormant ovarian cancer cells that persist after initial treatment only to reawaken years later, researchers at The University of Texas M. D. Anderson Cancer Center report in the December Journal of Clinical Investigation.
The team found that expression of a gene called ARHI acts as a switch for autophagy, or self-cannibalization, in ovarian cancer cells. Often a mechanism for cancer cell death, in this case "self-eating" acts as a survival mechanism for dormant cancer cells.
"Prolonged autophagy is lethal to cancer cells, but a little autophagy can help dormant cancer cells survive, possibly by avoiding starvation," said senior author Robert Bast, M.D., vice president for translational research at M. D. Anderson.
"Dormant cells are a major problem in ovarian cancer, breast cancer and other malignancies," Bast said. "We often see ovarian cancer removed, leaving no remaining sign of disease. After two or three years, the cancer grows back. If any remaining cancer cells had continued to grow normally, the disease should have returned in weeks or months.
"So the assumption is that some cells remain dormant without dividing and without developing a blood supply, but the mechanism for this has not been well understood," Bast said.
Bast and colleagues focused on ARHI, short for aplasia Ras homolog member I, a gene found in normal cells, but that is underexpressed in 60-70 percent of ovarian cancers.
When normal levels of ARHI were restored to ovarian cancer cells in the laboratory, autophagy was induced and cancer cells died within a few days.
When the experiments moved to human ovarian cancer grafts in mice, a different effect was noted. ARHI stopped tumor growth and induced autophagy, but did not kill the cancer cells. When ARHI was turned off at 4 to 6 weeks, the ovarian cancer cells grew rapid
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center