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Alternative mechanisms of action of anti-oestrogens


The molecular mechanism of action of anti-oestrogens such as tamoxifen appears to be a complex mixture of antagonism of the mitogenic action of oestradiol at the level of the oestrogen receptor, plus a range of other activities from enzyme inhibition to growth factor modulation. This article will concentrate on two specific areas: 1) the inhibition of protein kinase C and calmodulin-dependent cAMP phosphodiesterase; and 2) the regulation by tamoxifen of peptide regulators of breast cancer epithelial cell growth such as insulin-like growth factor I (IGF I) and transforming growth factor beta (TGF-β). The elucidation of these mechanisms is potentially important in the treatment and chemoprevention of breast cancer — the quantitative contribution of each individual mechanism of the overall antineoplastic action of anti-oestrogens is central to developing new and possibly more effective anti-oestrogens and optimizing strategies for their use.

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Correspondence to Anthony A. Colletta.

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Colletta, A.A., Benson, J.R. & Baum, M. Alternative mechanisms of action of anti-oestrogens. Breast Cancer Res Tr 31, 5–9 (1994).

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Key words

  • antiestrogens
  • cAMP phosphodiesterase
  • growth factors
  • insulin-like growth factors
  • protein kinase C
  • tamoxifen
  • transforming growth factor beta