The oestrogen-like effect of 4-hydroxytamoxifen on induction of transforming growth factor alpha mRNA in MDA-MB-231 breast cancer cells stably expressing the oestrogen receptor

Br J Cancer. 1998 Jun;77(11):1812-9. doi: 10.1038/bjc.1998.301.


Oestrogens and antioestrogens modulate the synthesis of transforming growth factor alpha (TGF-alpha) in breast cancer cells. The purpose of the present report was to examine regulation of TGF-alpha gene expression by oestradiol (E2) and antioestrogens in MDA-MB-231 breast cancer cells transfected with either the wild-type or mutant oestrogen receptor (ER). We recently reported the concentration-dependent E2 stimulation of TGF-alpha mRNA in MDA-MB-231 ER transfectants (Levenson et al, 1997). We now report that 4-hydroxytamoxifen (4-OHT) shows oestrogen-like effects on the induction of TGF-alpha gene expression in our transfectants. Accumulation of TGF-alpha mRNA in response to both E2 and 4-OHT but not in response to the pure antioestrogen ICI 182,780 suggests that E2-ER and 4-OHT-ER complexes can bind to an oestrogen response element (ERE), located in the promoter region of the TGF-alpha gene and can activate transcription of the gene. Surprisingly, no activation of luciferase expression was observed after transient transfection of the TGF-alpha ERE/luciferase reporter constructs. Possible activation of an alternative ER-mediated pathway responsible for the regulation of TGF-alpha gene expression in the ER transfectants is discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Dose-Response Relationship, Drug
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology*
  • Estrogens / pharmacology*
  • Female
  • Fulvestrant
  • Humans
  • RNA, Messenger / analysis*
  • Receptors, Estrogen / physiology*
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology
  • Transforming Growth Factor alpha / genetics*


  • Estrogen Antagonists
  • Estrogens
  • RNA, Messenger
  • Receptors, Estrogen
  • Transforming Growth Factor alpha
  • Tamoxifen
  • afimoxifene
  • Fulvestrant
  • Estradiol