Functional estrogen receptor beta in colon cancer cells

Evidence exists for expression of estrogen receptor beta (ER beta) in human colonic mucosa. Here we investigated the expression of the classical ER (E R alpha) and of four isoforms of the human ER beta in HCT116, HCT8, DLD-1, and LoVo colon adenocarcinoma cell lines. In addition, [3H]17 beta-estradio l (17 beta E-2) binding to intact colon cancer cells was evaluated. RT-PCR and Western blot analyses showed lack of expression of the classical ER alp ha in the four colon cancer cell lines. Conversely, wild-type ER beta isofo rm 1 was highly expressed in HCT8, HCT116, DLD-1, and LoVo cells and isofor ms ER beta 2-5 were present in HCT8 and HCT116 cells. Scatchard and Hill an alysis of [H-3]17 beta E-2, binding to the four different colon cancer cell s revealed the presence of two classes of binding sites, one with high affi nity (K-d values of 1-2 nM) and the other with lower affinity (K-d values o f 10-20 nM). Forty-eight hour-pretreatment of cells with 1 and 10 nM 17 bet a E-2 did not induce an increase of progesterone-specific binding to HCT8 c ells, while a significant induction was observed after treatment with 10 nM : 17 beta E-2 in HCT116 and DLD-1 cells and with both concentrations in LoV o cells. In addition, 1 pM-0.1 nM 17 beta E-2 significantly induced cell pr oliferation of HCT8 cells, while reducing growth of HCT116 and DLD1 cells a t 10 nM-1 mu M concentrations and of LoVo cells at all tested concentration s (1 pM-1 mu M). These in vitro findings pose the basis for in vivo functio ns of ER beta and ER beta-interacting molecules in human colon cancer tissu e. (C) 1999 Academic Press.