Study Finds Estrogen May Fuel Lung Cancer Growth

Long known to be instrumental in fueling the growth of breast cancer, estrogen may spur the same process in lung cancer, according to the findings of a University of Pittsburgh study presented at the annual meeting of the American Association for Cancer Research in San Francisco. The results are the first to directly demonstrate increased growth of non–small-cell lung cancer in the presence of estrogen.

More Estrogen Receptors on Lung Cancer Cells

“In our studies, we found greater numbers of estrogen receptors on lung cancer cells than on normal lung cells, strongly suggesting a role for this hormone in enhancing tumor growth,” said Jill Siegfried, PhD, principal investigator on the study and vice chairman of the department of pharmacology at the University of Pittsburgh. “These results are important in understanding how lung cancer affects women.”

Annually, lung cancer kills about 60,000 women in the United States. Non–small-cell lung cancer accounts for 80% of lung cancer cases. Some population studies have suggested that women develop the disease at an earlier age and with less tobacco exposure than do men, prompting scientists to search for biological reasons for these discrepancies. Investigations by Dr. Siegfried and others have indicated that there are fundamental differences in lung cancer between women and men, both in regard to the type of tumors that develop and the molecular mechanisms underlying the disease.

“Women have a naturally higher circulating estrogen level than men, and this difference may contribute to their increased susceptibility to lung cancer,” said Dr. Siegfried. “As in breast cancer, blocking the effects of estrogen could prove an important therapeutic strategy to halt disease progression or prevent recurrence. In addition, blocking estrogen receptors could prove beneficial in preventing lung cancer in women at high risk, much like blocking estrogen’s effect has been shown to prevent breast cancer in women at increased risk for that disease.”

Two Common Estrogen Receptors Examined

The study looked at two common estrogen receptors (ER-alpha and ER-beta) on lung cancer cell lines, cultured normal lung cells, and normal and tumor tissues from lung cancer patients. The researchers found that normal lung tissue rarely showed detectable levels of ER-alpha, whereas lung tumor cells had significantly higher levels of this receptor. ER-beta was found in both normal and tumor cells.

Treating cultured lung cancer cells with estrogen resulted in increased cell division, and estrogen given to animals with human lung cancers resulted in increased tumor growth. Antiestrogens inhibit this effect. Together, these results suggest that estrogen plays a role in lung cancer development.

Previous research conducted by Dr. Siegfried demonstrated that a gene for the protein gastrin-releasing peptide receptor is also more active in lung tissues in women than in men. This finding provides another possible biological reason for the observed differences in lung cancer between the sexes.