The retinoid X receptor-selective retinoid, LGD1069, prevents the development of estrogen receptor-negative mammary tumors in transgenic mice

Cancer Res. 2002 Nov 15;62(22):6376-80.

Abstract

Despite the effectiveness of the selective estrogen receptor (ER) modulators in preventing ER-positive breast cancer, chemopreventive agents still need to be developed for the prevention of ER-negative breast cancers. The naturally occurring retinoids are promising agents for the prevention of human cancers but are too toxic for long-term chronic use. We previously demonstrated that the chemopreventive effects of the retinoids could be separated from the toxicity by using an RXR-selective retinoid, LGD1069. The studies described here demonstrate that LGD1069 effectively suppresses ER-negative tumor development in mouse mammary tumor virus-erbB2 transgenic mice with minimal toxicity. These studies suggest that receptor-selective retinoids are promising agents for the prevention of breast cancer and that they may be particularly useful in preventing ER-negative breast cancer.

Publication types

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

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Bexarotene
  • Cell Division / drug effects
  • Female
  • Gene Expression / drug effects
  • Genes, erbB-2
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / prevention & control*
  • Mammary Tumor Virus, Mouse
  • Mice
  • Mice, Transgenic
  • Receptors, Estrogen / physiology
  • Receptors, Retinoic Acid / metabolism*
  • Retinoid X Receptors
  • Tetrahydronaphthalenes / pharmacology*
  • Transcription Factors / metabolism*
  • Transgenes / drug effects
  • Transgenes / genetics

Substances

  • Anticarcinogenic Agents
  • Receptors, Estrogen
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Tetrahydronaphthalenes
  • Transcription Factors
  • Bexarotene