SAN FRANCISCOIncreased circulating levels of the protein leptin, which
regulates body fat and fat mass, may be a risk factor for postmenopausal breast
cancer, according to a presentation at the 93rd Annual Meeting of the American
Association for Cancer Research (abstract 2503).
"These results clarify why women who are overweight are at greater risk
for breast cancer after menopause," said Margot P. Cleary, PhD, associate
professor, the Hormel Institute, University of Minnesota, Austin.
Leptin levels are known to increase in concert with increases in body weight
and mass. In previous experiments, scientists found that leptin is expressed in
mammary tissues and in some breast-cancer-derived cell lines. However, the
functional role of leptin in breast cancer progression is unknown, and leptin
receptors have not been identified in normal or cancerous mammary tissues.
Previous studies, however, have shown leptin receptors to be present in
lung, adrenal, stomach, and intestinal cancers, Dr. Cleary said.
To help elucidate leptin’s role in obesity and breast cancer, Dr. Cleary
and her colleagues did a series of in vivo and in vitro studies. They first
identified an active form of the leptin receptor that is present in both normal
and cancerous cells. The long form of the leptin receptor OB-Rb is expressed in
the HBL100 normal breast cell line and in the transformed estrogen-responsive
breast cancer cell line T-47D, they found.
When leptin was added to a medium in which normal HBL100 cells and T-47D
breast cancer cells were growing, both kinds of cells experienced enhanced
rates of growth. After 10 days in the presence of leptin, cell number was
enhanced in HBL100 cells by 56% and in T-47D cells by 160%, compared with
controls that were not stimulated with the fat-regulating protein.
When leptin was added to both normal and breast cancer cells, the scientists
noted the phosphorylation of downstream signaling proteins STAT3 and ERK in
both types of cell lines.