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 nonsmall-cell lung cancer in the presence
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
Annually, lung cancer kills about 60,000 women in the United States.
Nonsmall-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 estrogens 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.