The impact of 17beta-estradiol and
antiestrogens on
uterine cancer cells is poorly understood. The aim of this study was to determine the impact of 17beta-estradiol,
4-hydroxytamoxifen,
raloxifene and ICI 182 780 on the cell proliferation of six
uterine cancer cell lines: HeLa, HEC-1-A, KLE, RL-95-2, Ishikawa and EN-1078D. The effects of these compounds on the cell proliferation of the six
uterine cancer cell lines were studied in the presence and absence of
estrogens (
phenol red and serum deprivation of sex
steroids). In a general manner, 17beta-estradiol and
4-hydroxytamoxifen showed similarities in their effects whereas
raloxifene showed a different pattern of cell proliferation (agonistic and antagonistic) and ICI 182 780 had antagonistic activity. In the presence and absence of
estrogens, we observed that each cell line had diverse expression of
ERalpha,
ERbeta, GPR30 and REA. GPR30
mRNA expression was significantly reduced in a serum/
phenol-free medium. REA
mRNA expression was not influenced by the media. Results demonstrated the importance of removing
phenol red and the use of deprived serum when studying
uterine cancer cells in relationship with 17beta-estradiol and
antiestrogens. The affinity of each compound to the binding of
ERalpha and
ERbeta was very similar with the exception of
raloxifene that had a preference for
ERalpha binding. Akt phosphorylation/activity was reduced in cells cultured in a
phenol red- and
steroid-free culture medium indicating that the presence of
steroids in the
culture media can influence the activity of this survival pathway. Our results suggest that the expression of
ERalpha,
ERbeta and GPR30 are influenced by sex
steroids and might play a role in the response of cells to 17beta-estradiol and
antiestrogens but are not the only factors involved in this process.