Comparative profiling of the gene expression for estrogen responsiveness in cultured human cell lines.

It is important to know the difference as well as the similarity in estrogen responsiveness among cell lines for understanding the effects of estrogenic chemicals. Here, using 120 estrogen responsive genes, we examined comparative expression profiles between the profile in breast cancer MCF-7 cells treated with 17beta-estradiol and the profiles in other cell lines derived from breast (T-47D and HBC-4 cells), endometrium (Ishikawa cells) and kidney (RXF-631L cells) treated with estrogenic chemicals. First, comparative profiling between MCF-7 and T-47D cells showed similar (correlation coefficient or R value=0.49-0.87) profiles for all chemicals examined: 17beta-estradiol, estrone, estriol, diethylstilbestrol, bisphenol A, nonylphenol and genistein. The analysis using other cell lines indicated that significant correlations to the profile in MCF-7 cells treated with 17beta-estradiol were observed for the profiles in Ishikawa cells treated with 17beta-estradiol, diethylstilbestrol and bisphenol A, and HBC-4 cells treated with 17beta-estradiol. The profiles for diethylstilbestrol and bisphenol A in HBC-4 cells and all three chemicals in RXF-631L cells did not show significant correlation with those in MCF-7 cells. Hierarchical cluster analysis revealed that there are cell-specific responses to estrogenic chemicals (T-47D and HBC-4 cells for example). Correlation analysis using six (proliferation, transcription, transport, enzymes, signaling and others) functionally-categorized gene groups indicated that the genes related to enzymes showed greater correlations for all chemicals tested in T-47D cells and some chemicals in Ishikawa and HBC-4 cells while those related to transcription contributed to variations.