[Dynamic changes in estrogen receptor levels in the cell cycle of human endometrial adenocarcinoma studied by flow...

Normal endometrial cells and endometrial adenocarcinoma cells were doubly stained with 1-(N)-fluoresceinyl estrone thiosemicarbazone (17-FE) and propidium iodide and the contents of estrogen receptor (ER) and nucleic acids in a single cell were measured by flow cytometry to clarify the changes in ER levels in the cell cycle. In HHUA cells, established from a well differentiated endometrial adenocarcinoma, used as the ER positive tumor model, the cytoplasmic ER (cER) level increased 1.40 times in the S phase and nuclear ER (nER) level increased 1.65 times in the G2/M phase compared with the levels in the G1 phase. In normal endometrial cells, nER content gradually increased from the early proliferative phase to the ovulatory phase with 2.86 +/- 1.12 times higher levels in the G2/M phase than those in the G0G1 phase and remained high until the mid-secretory phase. Human endometrial adenocarcinoma could be classified into 3 types based on nER levels in G1 and G2/M phases; 1) adenocarcinoma with nER accumulation in G2/M phase as in normal proliferative endometrial cells, 2) adenocarcinoma with nER but with failure of nER accumulation in G2/M phase, suggesting acceptor deficiency, and 3) adenocarcinoma with no nER, suggesting a lack of cER and/or acceptor. These results suggest that cell cycle specific nuclear accumulation of ER, especially in the G2/M phase, is principally related to estrogen dependent proliferation of normal and neoplastic cells.