EFFECT OF RETINOID ANALOGS ON MAMMARY-CANCER IN TRANSGENIC MICE WITH C-NEU BREAST-CANCER ONCOGENE

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 st rategies to delay/prevent breast cancer. Fiber-rich nonpurified diet ( NTP-2000), as compared to a purified diet (AIN-76A), has previously be en shown to significantly delay the development of mammary cancer in t he 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 40-87 57 at 2 and 3 mmol/kg for 26 weeks. The 4-HPR at 5 mmol/kg diet delaye d the development of palpable tumors up to 24 weeks, but by 26 weeks, the incidence was not significantly different from the NTP-2000 diet c ontrol group, However, the 4-HPR diet markedly decreased the average w eight of the tumors at 26 weeks, The 4-HPR diet also caused a signific ant increase in body weight without an increase ill food consumption. Arotinoid Re-40-8757 at both doses inhibited the development of mammar y tumors for the duration of the study. However, the Ro 40-8757 at 3 m mol/kg appeared to be toxic as indicated by a significant depression o f 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 in hibitory effect on the development of mammary cancer than 4-HPR, Studi es to evaluate genetic changes and expression of hormonal receptors an d growth factors associated with the inhibition of mammary cancer deve lopment by the retinoid analogues are in progress.