Researchers at the Kimmel Cancer Center at Jefferson in Philadelphia have found new evidence suggesting that colon cancer is actually a disease of missing hormones that could potentially be treated by hormone replacement therapy.
Reporting August 1, 2007 in the journal Gastroenterology, clinical pharmacologist Scott Waldman, M.D., Ph.D., professor and chair of pharmacology and experimental therapeutics at Jefferson Medical College of Thomas Jefferson University, and his co-workers showed that GCC , guanylyl cyclase C, a protein receptor on the surface of intestinal epithelial cells for two hormones, guanylin and uroguanylin, can suppress tumor formation. These hormones regulate the growth of intestinal epithelial cells.
But early in colon cancer development, these growth-controlling hormones are ,lost, and not expressed, disrupting GCC's activity, and, Dr. Waldman believes, contributing to tumor formation. Using two separate mouse models that mimic the development of colon cancer in people, his team showed that GCC signaling blocks such tumors from forming.
According to Dr. Waldman, the group found that GCC stops tumors from forming through two different mechanisms. In one case, it controls cell growth, while in the other, it maintains ,regulation of genomic integrity."
In one mouse cancer model, the animals carried mutations in the APC gene, which causes colon polyps that frequently lead to colon cancer. Mice in the other cancer-development model were exposed to a commonly used experimental cancer-causing agent, azoxymethane. "We modeled both ways that humans develop colon cancer, and studied the effects of a lack of GCC on the incidence of colon cancer development," he explains.
"We found that in animals that have APC mutations, tumors developed in the colon and small intestine, which is expected," Dr. Waldman says. "A lack of GCC resulted in both larger tumors and a greater number of tumors in the large intestine." In the carcinogen model, the absence of GCC caused an increase in both tumor number and size also.