Gender difference in the activity but not expression of estrogen receptors α and β in human lung adenocarcinoma cells
- 1 March 2006
- journal article
- Published by Bioscientifica in Endocrine-Related Cancer
- Vol. 13 (1), 113-134
- https://doi.org/10.1677/erc.1.01118
Abstract
The higher frequency of lung adenocarcinoma in women smokers than in men smokers suggests a role for gender-dependent factors in the etiology of lung cancer. We evaluated estrogen receptor (ER) α and β expression and activity in human lung adenocarcinoma cell lines and normal lung fibroblasts. Full-length ERα and ERβ proteins were expressed in all cell lines with higher ERβ than ERα. Although estradiol (E2) binding was similar, E2 stimulated proliferation only in cells from females, and this response was inhibited by anti-estrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780. In contrast, E2 did not stimulate replication of lung adenocarcinoma cells from males and 4-OHT or ICI did not block cell proliferation. Similarly, transcription of an estrogen response element-driven reporter gene was stimulated by E2 in lung adenocarcinoma cells from females, but not males. Progesterone receptor (PR) expression was increased by E2 in two out of five adenocarcinoma cell lines from females, but none from males. E2 decreased E-cadherin protein expression in some of the cell lines from females, as it did in MCF-7 breast cancer cells, but not in the cell lines from males. Thus, ERα and ERβ expression does not correlate with the effect of ER ligands on cellular activities in lung adenocarcinoma cells. On the other hand, coactivator DRIP205 expression was higher in lung adenocarcinoma cells from females versus males and higher in adenocarcinoma cells than in normal human bronchial epithelial cells. DRIP205 and other ER coregulators may contribute to differences in estrogen responsiveness between lung adenocarcinoma cells in females and males.Keywords
This publication has 88 references indexed in Scilit:
- Lung Cancer in WomenJournal of Clinical Oncology, 2005
- A Randomized Trial of Exemestane after Two to Three Years of Tamoxifen Therapy in Postmenopausal Women with Primary Breast CancerNew England Journal of Medicine, 2004
- K-ras Gene Mutation Enhances Motility of Immortalized Airway Cells and Lung Adenocarcinoma Cells via Akt Activation: Possible Contribution to Non-Invasive Expansion of Lung AdenocarcinomaThe American Journal of Pathology, 2004
- Response element sequence modulates estrogen receptor alpha and beta affinity and activityJournal of Molecular Endocrinology, 2002
- Cooperative Coactivation of Estrogen Receptor α in ZR-75 Human Breast Cancer Cells by SNURF and TATA-binding ProteinPublished by Elsevier BV ,2002
- Women and lung cancer: does oestrogen play a role?The Lancet Oncology, 2001
- Cofactor Dynamics and Sufficiency in Estrogen Receptor–Regulated TranscriptionCell, 2000
- Comparison of transcriptional synergy of estrogen receptors α and β from multiple tandem estrogen response elementsMolecular and Cellular Endocrinology, 2000
- Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption.JCI Insight, 1997
- Androgens inhibit basal and estrogen-induced cell proliferation in the ZR-75-1 human breast cancer cell lineBreast Cancer Research and Treatment, 1988