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Effect of retinoid analogues on mammary cancer in transgenic mice with c-neu breast cancer oncogene.

Abstract
Breast cancer is one of the most common cancers and is a leading cause of mortality in women. The TG.NK transgenic mouse line expresses the c-neu breast cancer oncogene under the control of an MMTV promoter and appears to be a useful animal model for evaluation of intervention strategies to delay/prevent breast cancer. Fiber-rich nonpurified diet (NTP-2000), as compared to a purified diet (AIN-76A), has previously been shown to significantly delay the development of mammary cancer in the TG.NK model. Four-week old hemizygous TG.NK female mice with MMTV/c-neu oncogene were fed NTP-2000 diet containing the retinoid analogue 4-hydroxyphenyl retinamide (4-HPR) at 5 mM/kg or an arotinoid Ro 40-8757 at 2 and 3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delayed the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet control group. However, the 4-HPR diet markedly decreased the average weight of the tumors at 26 weeks. The 4-HPR diet also caused a significant increase in body weight without an increase in food consumption. Arotinoid Ro-40-8757 at both doses inhibited the development of mammary tumors for the duration of the study. However, the Ro 40-8757 at 3 mmol/kg appeared to be toxic as indicated by a significant depression of the average body weight with alopecia and skin scaling in some mice. Our observations with TG.NK transgenic mouse and fiber-rich diet (NTP-2000) indicate that the arotinoid Ro 40-8757 has a markedly higher inhibitory effect on the development of mammary cancer than 4-HPR. Studies to evaluate genetic changes and expression of hormonal receptors and growth factors associated with the inhibition of mammary cancer development by the retinoid analogues are in progress.
AuthorsG N Rao, E Ney, R A Herbert
JournalBreast cancer research and treatment (Breast Cancer Res Treat) Vol. 48 Issue 3 Pg. 265-71 (Apr 1998) ISSN: 0167-6806 [Print] Netherlands
PMID9598873 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anticarcinogenic Agents
  • Morpholines
  • Retinoids
  • Fenretinide
  • mofarotene
Topics
  • Animals
  • Anticarcinogenic Agents (therapeutic use)
  • Female
  • Fenretinide (therapeutic use)
  • Genes, erbB-2 (genetics)
  • Mammary Neoplasms, Animal (genetics, prevention & control)
  • Mice
  • Mice, Transgenic
  • Morpholines (therapeutic use)
  • Retinoids (therapeutic use)

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