"If you give a cancer-causing agent to animals, what you see is that the cells start proliferating more, and in common with that we see an increase in Kinase C beta II expression," says Alan P. Fields, senior author. "If you feed the animals an omega-3 fatty acid you blunt that proliferative response. The hypothesis was that Kinase C beta II caused hyperproliferation and increased sensitivity to carcinogens, and that it was the target for the omega-3 fatty acid."

To test that hypothesis, Fields and Nicole R. Murray, lead author, created genetically modified mice whose colon cells over-produced the kinase protein. These transgenic rodents were far more likely to develop colon cancer when exposed to a known carcinogen than were normal mice, and they showed evidence of the runaway cell growth that precedes cancer even when not exposed to any carcinogen. Giving transgenic mice a diet high in omega-3 fatty acids, however, reduced their risk of colon cancer to that of normal mice, and the mice on the omega-3 diet also exhibited no runaway growth of colon cells.

"We found that the hyperproliferation, which we normally see in these transgenic animals, is completely blocked by omega-3 fatty acids," Fields says. "And furthermore, now when we expose these animals to a carcinogen, they have the same cancer risk as non-transgenic mice."

In addition to determining that omega-3 fatty acids inhibit the carcinogenic action of the protein in mice, the scientists also used cell cultures derived from rat intestines to explore how the protein causes hyperproliferation. Cells with a high intracellular protein level produced much less of a substance known as transforming growth factor beta receptor type II (TGFbRII), a molecule critical to controlling cell reproduction under control. Examination of colon cells from transgenic mice not given omega-3 fatty acids revealed that they, too, lacked the receptor -- but colon cells from transgenic mice fed omega-3 fatty acids had the receptors in abundance.

"Just as in the cell lines in which we over-expressed Protein Kinase C beta II and the transforming growth factor beta receptor type II levels were suppressed, we saw the same effect in our transgenic mice," Fields says. "But then when we fed them an omega-3 fatty acid diet, we inhibited the kinase, and receptor levels came back up. So there's a reversal in this high-risk animal."

Fields points out that low levels of the growth factor receptor have also been observed in many other cancer cell types, including breast cancer, gastric cancer, small-cell lung cancer, esophageal cancer, liver cell carcinoma, bladder cancer, squamous cell carcinoma, endometrial cancer and osteosarcoma. Taken together with the observation that omega-3 fatty acids also seem to prevent breast and prostate cancer, he notes, this suggests that the kinase may play a significant role in more than just colon cancer -- and that inhibiting its action, either through diet or drugs, could help prevent and treat a broad range of diseases.