Expression, function, and clinical implications of the estrogen receptor β in human lung cancers

The higher frequency of human lung adenocarcinoma in females than in males, strongly suggests the involvement of gender dependent factors in the etiology of this disease. This is the first investigation of estrogen receptor (ER) β in human lung. Immunohistochemical staining revealed ERβ expression in normal lung and in atypical adenomatous hyperplasia (AAH), considered as a precancerous lesion for adenocarcinomas. Adenocarcinomas showed significantly higher expression of ERβ than squamous cell carcinomas. On the contrary, ERα expression was not detected in all cases. The functional integrity of ERβ such as the binding ability to estrogen responsive element (ERE) and transcriptional activity was confirmed using a human lung cancer cell line, RERF-LC-OK. Colony formation of this cell was significantly reduced in the presence of pure antiestrogen. We conclude that ERβ, but not ERα, is present in lung tissues with an important physiological function in normal lung. Furthermore, ERβ may play a role in growth and development of adenocarcinomas.