Dietary regulation of mammary tumorigenesis in RIII/Sa mice: investigation of a possible mechanism.

Abstract

The effects of caloric restriction on the incidence of mammary tumor development, the levels of the expression of mouse mammary tumor virus (MMTV)- and prolactin-RNA, as well as the levels of serum prolactin, were investigated in virgin RIII/Sa mice, a strain known to display a high incidence of spontaneous mammary tumor development. Of the 54 mice fed a low-calorie (LC; 10 kcal/day) diet containing low fat (LF; 5% corn oil) for a period of 72 weeks, only seven mice were found to develop mammary tumors, an incidence of 13%. By contrast, the cumulative tumor incidence in a similar sized group of mice, fed a high-calorie (HC; 16 kcal/day) low fat-containing diet was 73%. Estimation of the relative levels of MMTV-RNA, as determined by Northern and slot blot hybridizations, in the mammary glands of mice fed LCLF and HCLF diets for 8, 10, 16, 28, and 36 weeks revealed that the LCLF diet-fed mice expressed 4-15-fold less RNA than the HCLF diet-fed mice. Interestingly, however, the LCLF diet did not appear to exert any effect on the expression of prolactin RNA even though it reduced the levels of serum prolactin. We suggest that in RII/Sa mice the modulation of MMTV-induced mammary tumors by dietary calorie is linked to the secretion of serum prolactin which, in turn, affects the replication of MMTV required for mammary cell transformation.