title: Oestetrol stimulates proliferation and oestrogen receptor expression in breast cancer cell lines: comparison of four oestrogens.
abstract: OBJECTIVE
  Oestetrol (15-alpha-hydroxyoestriol, E₄) is an endogenous oestradiol metabolite mainly produced at high concentrations in the fetal liver. In earlier studies E₄ was investigated for its use as marker for pregnancies at risk, especially with vascular problems. Some current investigations suggest that the use of E4 in hormone therapy or contraception may have advantages in terms of breast cancer risk when compared to other oestrogens.
  
  
  METHODS
  Proliferation of two oestrogen receptor-positive breast cancer cell lines (ZR 75-1 and HCC 1500) was investigated after incubation with oestrone (E₁), oestradiol (E₂), oestriol (E₃), and oestetrol (E₄). Receptor expression of oestrogen receptor-alpha (ERα) and -beta (ERβ) was determined by Western-Blot.
  
  
  RESULTS
  All four oestrogens elicited a significant proliferative stimulation at concentrations of 10(-10) und 10(-9) M as compared to controls. Oestrone displayed a significantly weaker effect than E₂. Oestetrol was significantly less effective than E₂ at the lower concentration. Expression of ERα and ERβ was significantly upregulated by all oestrogens tested, without differences between the latter.
  
  
  CONCLUSIONS
  Our results indicate a slightly lower proliferative effect of E₄, but only at low concentrations. However, no difference was found regarding receptor expression. Breast cancer risk associated with use of oestetrol should be tested in clinical trials.
authors.affiliation: * Department of Gynaecological Endocrinology, Beijing Obstetrics and Gynaecology Hospital, Capital Medical University , Beijing , China.
authors.forename: Shunyu
authors.initials: S
authors.lastname: Liu
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Ruan
authors.forename: Silke
authors.initials: S
authors.lastname: Schultz
authors.forename: Hans
authors.initials: H
authors.lastname: Neubauer
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Mueck
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004953:Estetrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000235:genetics / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D011980:Receptors, Progesterone; D004970:Estrone; D004958:Estradiol; D004953:Estetrol; D004964:Estriol
keywords: Breast cancer; Contraception; Estetrol; Hormone replacement therapy; Oestetrol