Functional estrogen receptor beta in colon cancer cells

Biochem Biophys Res Commun. 1999 Aug 2;261(2):521-7. doi: 10.1006/bbrc.1999.1062.

Abstract

Evidence exists for expression of estrogen receptor beta (ERbeta) in human colonic mucosa. Here we investigated the expression of the classical ER (ERalpha) and of four isoforms of the human ERbeta in HCT116, HCT8, DLD-1, and LoVo colon adenocarcinoma cell lines. In addition, [(3)H]17beta-estradiol (17betaE(2)) binding to intact colon cancer cells was evaluated. RT-PCR and Western blot analyses showed lack of expression of the classical ERalpha in the four colon cancer cell lines. Conversely, wild-type ERbeta isoform 1 was highly expressed in HCT8, HCT116, DLD-1, and LoVo cells and isoforms ERbeta2-5 were present in HCT8 and HCT116 cells. Scatchard and Hill analysis of [(3)H]17betaE(2) binding to the four different colon cancer cells revealed the presence of two classes of binding sites, one with high affinity (K(d) values of 1-2 nM) and the other with lower affinity (K(d) values of 10-20 nM). Forty-eight hour-pretreatment of cells with 1 and 10 nM 17betaE(2) did not induce an increase of progesterone-specific binding to HCT8 cells, while a significant induction was observed after treatment with 10 nM 17betaE(2) in HCT116 and DLD-1 cells and with both concentrations in LoVo cells. In addition, 1 pM-0.1 nM 17betaE(2) significantly induced cell proliferation of HCT8 cells, while reducing growth of HCT116 and DLD1 cells at 10 nM-1 microM concentrations and of LoVo cells at all tested concentrations (1 pM-1 microM). These in vitro findings pose the basis for in vivo functions of ERbeta and ERbeta-interacting molecules in human colon cancer tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism*
  • DNA Primers / genetics
  • Estradiol / pharmacology
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Gene Expression
  • Humans
  • Kinetics
  • Neoplasms, Hormone-Dependent / etiology
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • DNA Primers
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Estradiol