Health Leader: Double Jeopardy - The Link between estrogen and insulin

STORY BY

Nora K. Shire

When two normally occurring hormones are brew together, the effects on women could turn dangerous, scientists have discovered.

When the hormones insulin and estrogen interact, the result is the growth and proliferation of breast cancer cells. Women with diabetes are more likely to get breast cancer, and women with breast cancer are more likely to get diabetes.

What Dr. Victoria Knutson found in her initial lab experiments is that "when breast cancer cells are bathed in estrogen, as occurs in pre-menopausal women, the cells are more sensitive to insulin, which stimulates growth."

Knutson is associate professor in the Department of Integrative Biology and Pharmacology at The University of Texas Medical School at Houston.

"We now know that there is interaction between estrogen and insulin signaling," she says. From her research, the insulin is not causing breast cancer, but it encourages growth in already existing cancer cells.

In the lab, Knutson says, breast cancer cells treated with insulin alone have no impact on the growth of the cells. When breast cancer cells are treated with estrogen, it induces growth. "However, if we add both together, there is a synergy, and we have amplified growth. That amplification increases with higher concentrations of insulin. More insulin is worse," she says and adds, "the impact then for a diabetic woman is horrible."

In a woman who does not have diabetes, the insulin level rises each time she eats and within two hours goes back down. If there is a snack, it shoots up and down quickly. But, with the diabetic, that insulin level goes up and stays there.

If the woman is pre-menopausal, estrogen is also present. Consequently, estrogen in the presence of steadily elevated insulin has an impact on breast cancer growth.

In the 1970s Knutson says, there were studies that demonstrated that diabetic women had a two-to three-fold higher risk for getting breast cancer. "Finding one factor with such a risk is significant."

LAR: Mystery Molecule

Breast cancer growth is a complicated puzzle. Knutson is studying one of the pieces, a molecule called LAR, which deactivates the insulin receptor.

LAR has been implicated in diabetes because it helps to turn off the insulin signal. "Although we don't know why, LAR also has been linked to breast cancer that has metastasized or spread to distant sites in the body," she explains.

"We were looking at breast cancer in diabetics, and there was LAR again. It is important because breast cancer cells treated with estrogen decreased the expression of the LAR molecule. This means that the insulin receptor is super active and helps promote the growth of the cancer, even in the absence of insulin. So just by treating the cells with estrogen, we turned on the insulin pathway."

One big question Knutson has is LAR's function in metastasis—the spread of cancer to other parts of the body. Knutson plans to work with the UT M. D. Anderson Cancer Center to study tissue taken from women with breast cancer, both pre-metastatic and metastatic (both localized and spreading breast cancer) tissue.

Looking for New Predictors

"There are tests to identify a person in a pre-diabetic state. We already know that a woman with gestational (while pregnant) diabetes is at risk for developing the disease when she is older. Both African-Americans and Hispanics have a predisposition for diabetes," Knutson says. "Except for family history, there is no good predictor for breast cancer. So, if a woman has a family history of both diabetes and breast cancer, that should put her on notice."

By looking at the level and location of LAR she hopes to understand the role of the molecule and if it could be used as a predictor or risk factor for metastatic breast cancer, especially in women who are at risk for diabetes.

Knutson fervently believes that a diabetic woman should be vigilant about being tested for breast cancer or at least have the recommended mammograms for her particular age.

Last Updated: 1-11-2005

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About Dr. Knutson:

Dr. Victoria Knutson is an associate professor in the Department of Integrative Biology and Pharmacology at the UT Medical School.

See Dr. Knutson also at:

Double Jeopardy

Health Tip:

Packing Bag Lunches Safely

If you pack lunches for your child to take to school, be careful that you do not accidentally expose them to foodborne illness.

Bagged lunches, especially those containing perishable foods, need to be packed and handled properly in order to keep the food safe. In general, perishable foods should not be left at room temperature for more than two hours. If left out too long, the temperature of the food can enter the danger zone where bacteria grow most rapidly, which is between 40 and 140 degrees Fahrenheit.

Below are some tips to help families pack bagged lunches safely:

Pack foods that are nonperishable and won't require refrigeration.
If you do pack perishable foods such as luncheon meats or prepackaged cheese and crackers, include a frozen gel pack or a frozen juice carton with the food in an insulated lunch bag or box.
Pack only the amount of perishable food that your child can eat at lunch.
Preparing lunches the night before and storing them in the refrigerator until you pack your child's lunchbox in the morning can help keep food cold longer the next day.
Don't reuse packaging materials such as paper or plastic bags, aluminum foil, etc. as they can contaminate other foods and cause foodborne illness. Have your child discard all used food packaging and paper bags after lunch.

Before eating lunch or snacks at school, make sure your child washes his or her hands with soap and warm water for at least 20 seconds. If your child's school does not have a handwashing program in place, encourage them to adopt a such a program, as handwashing is one of the best ways kids and parents can protect health and stop the spread of germs.