Researchers 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.
The findings indicate that the mechanism of the increase in tumor development through loss of GCC expression was a combination, in both models, of a loss of genomic integrity and an increase in cell growth. “When you eliminate GCC from cells, they develop a level of genomic instability, where they start accumulating more mutations and lose pieces of genetic material,” he explains.
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The finding “converts colon cancer from a genetic disease, which is the way we’ve all thought about it, to a disease of hormone insufficiency,” Dr. Waldman says. “It’s a completely different way of thinking about the disease.
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Essentially, this takes the genetic disease and converts it to an endocrine disease, with a hormone solution.” The researchers would like to extend these studies to show that by treating patients with hormone replacement therapy, intestinal cancer formation can either be prevented or treated.
Source-Eurekalert
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