Submitted to: Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/27/2006
Publication Date: 5/15/2007
Citation: Su, Y., Eason, R.R., Till, R.S., Badger, T.M., Simmen, R.C. 2007. In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis. Carcinogenesis. 28(5):1046-1051.
Interpretive Summary: Mammary cancer is caused by many factors, and diet is one factor that can influence the initiation and/or progression of this disease. We have shown in the present study using a rat model, that consumption of soy protein isolate, the only protein present in soy infant formula, by pregnant mothers may protect their offspring from mammary cancer during adult life. Thus, while it is well known that diet and nutritional status during pregnancy are important and can influence the course of the pregnancy and the development of the fetus, we are now learning more about how dietary factors may affect the health of offspring later in life, i.e. as adults. For example, early dietary factor exposure may prevent diseases that occur later in life, such as breast cancer. Although much more research is required on this topic, pregnant mothers should seriously consider the type of foods they consume during pregnancy, since proper nutrition during early stages of fetal development can positively or negatively affect the health status at adulthood.
Technical Abstract: The linkage of nutrition and cancer prevention is an intriguing concept that is gaining widespread support, based on cumulative data from epidemiological and laboratory studies demonstrating the anti-carcinogenic actions of numerous dietary constituents. We previously reported tumor protection by lifetime exposure to diets containing the soy isoflavone genistein (GEN) in a rat model of mammary carcinogenesis. Here, we investigated the influence of developmental context on dietary protection against tumor incidence and progression initiated by the direct-acting carcinogen N-methyl-N-nitrosourea (NMU), and examined potential mechanisms underlying these effects. Rats were exposed only in utero or for lifetime to AIN-93G diets made with casein (CAS), soy protein isolate (SPI) or CAS supplemented with GEN (CAS+GEN). Mammary glands of postnatal day (PND) 50 rats prior to NMU administration were examined for apoptotic status, pro-apoptotic gene expression, and immunoreactive PTEN and E-cadherin levels, while mammary tumor parameters were evaluated 99 days post-NMU. Animals exposed only in utero to SPI had increased tumor latency and decreased tumor multiplicity and tumor grade, than those fed the control diet CAS. By contrast, in utero exposure to supplemental GEN resulted in similar tumor parameters as the CAS group, while lifetime SPI exposure decreased tumor incidence that was not mimicked by in utero exposure alone. Mammary glands of PND50 rats fed lifetime SPI had increased apoptotic status and PTEN expression, relative to the other diet groups. Rats exposed only in utero to SPI or CAS+GEN had higher membrane E-cadherin in mammary structures than those lifetime fed CAS or SPI. Results indicate that limited exposure during gestation to soy proteins can positively influence resistance to chemically induced mammary tumorigenesis later in life and suggest that strategic approaches for the prevention of mammary and other types of cancer might be uncovered by careful refinement of the developmental window for specific dietary factor exposure.