This month, Dr. Sydney Spiesel discusses new research that saves mice from breast cancer, the life-extending properties of red wine, the risks of long-distance running, and an unwelcome new cause of anemia in the Third World. For his last two columns, please click here and here.
Breast cancer—new hope?
Question: Does progesterone, the hormone of pregnancy, play some role in the development or progression of breast cancer? There is some evidence that the answer is yes. Now research may point the way toward blocking the role the hormone plays in developing tumors in women at high risk of developing breast cancer because of a genetic predisposition.
Gene: Sometimes breast cancer runs in families, controlled by one or more genes. The best-known of these is the gene BRCA1 ("breast cancer 1"). For most of us, this gene serves a powerful protective function, stabilizing our genetic structure by controlling a mechanism that repairs broken strands of DNA and, thus, reversing changes that would otherwise cause gene mutation. But the BRCA1 gene is itself subject to mutation. And certain of these (including a mutation found fairly frequently among Ashkenazic Jews) weaken the gene's customary protective effect. In addition, there is increasing evidence that BRCA1 regulates the effect of hormones on normal and malignant tissues. About one woman in 800 carries an abnormal BRCA1 gene; these women are at great risk for developing breast or ovarian cancer.
Experiment: Using the tools of genetic engineering, scientists can produce mice with a completely inactive BRCA1 gene, in effect mimicking a BRCA1 gene with a severe mutation—exactly the condition we encounter in women at high risk for breast and ovarian cancer. For reasons that aren't known, the breast tissue of these mice develops like the breast tissue of normal pregnant mice but is extra sensitive to the hormone progesterone. Every one of these BRCA1 "knockout" mice goes on to develop breast cancer before 9 months of age.
Findings: A research group headed by Aleksandra Poole and Eva Lee at the University of California at Irvine reasoned that progesterone might be playing a role in this tumor development. So they tried administering a medication, mifepristone. Also known as RU-486, * mifepristone blocks the action of progesterone. Poole and Lee's team were far more successful than they ever imagined: Not a single mifepristone-treated mouse developed breast cancer. Results this clear and dramatic are rare in science.
Conclusion: It is way too early to take this treatment from mice to humans, but it is an extraordinarily attractive research lead. I'm sure the search is already under way for suitable progesterone-blocking drugs for humans. The prospect of blocking the terrible effect of some mutant versions of the BRCA1 gene is exciting indeed.
Living forever while drinking red wine
New research: Living long and living well have always seemed to be mutually exclusive. Eat oysters and sweetbreads and expect your big toe to swell with gout. Limit your diet to a notch north of starvation and you might live longer. Now there is some evidence that calls these axioms into question. A research group headed by Joseph Bauer and David Sinclair (of Harvard Medical School) and Raphael de Cabo (of the National Institute on Aging) has reported on a treatment using a chemical found in red wine that insulates overindulgent mice from the effects of dietary excess. The chemical, resveratrol, had been shown to extend the life expectancy—and sometimes improve the health—of yeast cells, tiny worms, fruit flies, and fish. The research conducted on these simple organisms suggests that resveratrol may extend life span through the same mechanism that semi-starvation can.
Findings: The new research showed that when a middle-aged mouse was made obese on a fat-enriched diet and then treated with resveratrol, the chemical increased its life span, mimicking the expected effect of switching to a calorie-deficient diet. Administering resveratrol to half of the fat mice didn't slim them down (well, maybe it did a tiny bit, but they were still chunksters). The treatment did, however, increase their life spans to those of normal-weight mice. And it prevented many of the complications we are used to seeing in animals and humans on high-fat diets—poorly functioning fatty livers and resistance to insulin, which results in Type II diabetes. Thus, in this study resveratrol didn't prevent the overindulged mice from becoming fat. But it protected the fat mice from the expected change in their metabolism that leads to diabetes and, in addition, extended their lifespan beyond the expected.