A new study from the Fox Chase Cancer Center (FoxChaseCancerCenter) has found that a nutrient in carrots and sweet potatoes may be the key to early treatment of breast cancer. Fox? Sandra Fernandez, PhD, assistant research professor at the Chase Cancer Center, will publicly present the findings at the American Association for Cancer Research (AACR) 102nd Annual Meeting 2011 on Tuesday, April 5. Retinoic acid, a derivative of vitamin A, is considered a promising anti-cancer drug because of its ability to affect cell growth, reproduction and survival. Although retinoic acid is being tried in many clinical trials, its success in fighting cancer has not been very consistent so far. However, Fernandez and her colleagues have identified the key to retinoic acid’s mode of action – an important step toward the development of a successful therapeutic agent, most likely. Retinoic acid attaches to retinoic acid receptor-β (RAR-β), and it is perhaps through this mode of behavior that it is able to inhibit tumors. Decreased levels of retinoic acid receptor-β (RAR-β) in tumors correlate with cancer cell growth, while increased levels of retinoic acid receptor-β (RAR-β) correspond to a positive response of cancer cells to clinical interventions. The researchers suggest that the activated receptor may limit cell growth by regulating gene expression, but they do not fully understand the underlying mechanisms. However, to find the specific conditions under which retinoic acid inhibits or even reverses the growth of abnormal material in the breast, Fernandez invented a culture system that contains four cell lines representing different cancer stages: normal human breast cells; transformed cells (which cause breast lumps to grow when exposed to carcinogens); infiltrating cells (which can break through breast tissue barriers and spread to other parts of the body); and tumor cells (which form when infiltrating cells are injected into the mammary fat pad of mice and exhibit all the characteristics of malignant breast cancer cells). ”We found that the retinoic acid receptor-β (RAR-β) gene is very active in the first two stages of the cancer, but it falls silent in the last two stages.” Fernandez said, “These shifts in gene activation are caused by a chemical change called methylation, which is the addition of methyl groups inside the DNA.” In a three-dimensional culture system containing a collagen matrix, normal cells formed tubules that looked like normal mammary glands, while transformed cells produced clusters. Fifteen days after receiving retinoic acid, cells that produced clumps in collagen began producing tubules. In contrast, infiltrating cells and tumor cells that received retinoic acid treatment – even after concomitant treatment with a drug that activates retinoic acid receptor-β (RAR-β) by inhibiting DNA methylation – did not produce tubules. These findings suggest that retinoic acid can inhibit tumor growth in the early stages, but is ineffective in the later stages, when the genetic changes associated with cancer have become too drastic. “It seems that when the tumor progresses to a later stage, there is no way to reverse it with retinoic acid.” Fernandez said. The study also showed that the degree of methylation of retinoic acid receptor-β (RAR-β) could be used as a biological indicator for early diagnosis of breast cancer. In addition, drugs that reactivate the receptor by reducing DNA methylation could also help breast cancer patients. These treatments have been used to control one type of leukemia, so they are promising to be approved for other diseases as well.