Submitted to: Cancer Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2004
Publication Date: 12/13/2004
Citation: Simmen, R.C., Eason, R.R., Till, R.S., Chatman, L., Velarde, M.C., Geng, Y., Korourian, S., Badger, T.M. 2004. Inhibition of nmu-induced mammary tumorigenesis by dietary soy. Cancer Letters. 224(1): 45-52. Interpretive Summary: We have previously demonstrated that soy protein isolate, the soy protein form that is used in infant formula, prevents a large percentage of experimentally-induced breast cancer in rats. The cause of breast cancer is unknown, but clearly involves carcinogens and there are many known such agents that act in different ways. In this study, we tested whether soy proteins can protect against development of mammary cancer caused by the chemical carcinogen NMU. We report that lifetime diet of soy can confer cancer protection in young adult female rats. This study has important implications for women because it demonstrates that a “direct-acting” carcinogen that causes mammary cancer can be partially blocked in rats that consume a diet containing soy proteins
Technical Abstract: We previously demonstrated that female Sprague-Dawley rats fed AIN-93G diets containing soy protein isolate (SPI+) had lower DMBA-induced mammary tumor incidence than those fed diets containing casein (CAS), due partly to altered Phase I metabolism with soy. Here, we evaluated the tumor protective effects of these same diets to the direct-acting carcinogen N-methyl-nitrosourea (NMU). Tumor incidence was reduced and tumor latency was enhanced, in NMU-administered female rats lifetime exposed to SPI+, relative to the CAS group. Tumor multiplicity did not differ with diet, while tumor grade tended to be more advanced with SPI+. Normal mammary glands of CAS and SPI+ tumor-bearing rats had comparable proliferative and apoptotic status. However, mammary expression of HER-2/neu and progesterone receptor (PR) genes was higher for SPI+ rats. Moreover, tumor-bearing SPI+ rats had lower serum progesterone levels than those fed CAS, while serum estrogen did not differ. Serum from tumor-bearing SPI+ rats had higher apoptotic activity towards mammary epithelial MCF-7 cells, than CAS serum. Thus, dietary soy protects against mammary tumorigenesis induced by a direct-acting carcinogen and alters signaling pathways involving PR and HER-2/neu.