Serum estrogen level and tumor aromatase expression exhibit an inverse association with poor prognosis of lung adenocarcinoma, suggesting that estrogen plays a role in promoting this cancer. Exposure to exogenous estrogen is expected to increase the risk of lung adenocarcinoma. Secondhand cigarette smoke, a major environmental risk factor for never smokers, contains vast amounts of aromatic compounds in the particulate phase. In this study, we examine whether the extract of cigarette sidestream smoke particulates (CSSP) has estrogenic and/or antiestrogenic effects in lung adenocarcinoma cells. Our results demonstrate that the CSSP extract contains a dose-dependent estrogenic effect and activates ERα cumulatively with 17β-estradiol (E2) in lung adenocarcinoma cells. ICI 182,780 antagonizes CSSP-induced ERα transcriptional activity as well as that induced by E2. However, the CSSP extract regulates the nuclear entry, serine phosphorylation, and protein degradation of ERα in a similar but different manner from E2. As compared with E2 and ICI 182,780, ERα is rather stable under the CSSP treatment, suggesting that CSSP has a long-lasting estrogenic effect.
