Download The Role of Environmental Estrogens on Human Lung

CELL AND MOLECULAR BIOLOGY
Cadmium Chloride and Sodium Arsenate, Environmental Estrogens in Cigarette Smoke, Activate the
Estrogen Signaling Pathway to Induce Proliferation in a Human Lung Adenocarcinoma Cell Line. SARAH
L. TODD1*, ALISON S. BLESER1, KRISTA A. RIGGS2, SUSAN M. DOUGHERTY2, CAROLYN M.
KLINGE2 and MARY O. HUFF1. 1Department of Biology, Bellarmine University, Louisville, KY 40205
and 2Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine,
Louisville, KY 40202.
Of the 63 carcinogens in cigarette smoke, cadmium chloride and sodium arsenate are considered
environmental estrogens because they mimic the effect of estradiol in living systems. Since recent studies
support a role for estrogen in the etiology and progression of lung cancer, we wanted to determine if these
environmental estrogens could stimulate cellular proliferation in a similar manner. Treatment of a femalederived adenocarcinoma line, H1793, for 4 days with nanomolar concentrations of cadmium chloride or
sodium arsenate induced cellular proliferation similar to that seen for estradiol. Furthermore, inhibition of
the estrogen signaling pathway using an estrogen receptor antagonist ICI 180,780 partially reduced the
observed proliferation, supporting the involvement of the estrogen receptor signaling pathway. To
determine if these environmental estrogens can directly activate transcription of estrogen responsive genes,
cells were transfected with an estrogen response element driven luciferase reporter gene and treated for 30
hr with estradiol, cadmium chloride or sodium arsenate. The results indicate that, like estradiol, cadmium
chloride and sodium arsenate activate transcription. To determine the endogenous gene responses induced
by these environmental estrogens, RNA is being isolated after treatment and the expression of a battery of
estrogen-responsive genes will be analyzed.