Carcinogenesis Advance Access originally published online on December 13, 2006
Carcinogenesis 2007 28(5):1046-1051; doi:10.1093/carcin/bgl240
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In utero exposure to maternal diets containing soy protein isolate, but not genistein alone, protects young adult rat offspring from NMU-induced mammary tumorigenesis
1 Arkansas Children's Nutrition Center
2 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, 1120 Marshall Street, Little Rock, AR 72202, USA
* To whom correspondence should be addressed. Tel: +1 501 364 2849; Fax: +1 501 364 3161; Email: simmenrosalia{at}uams.edu
The linkage of nutrition and cancer prevention is an intriguing concept that is gaining widespread support. Here, we investigated the influence of developmental context on dietary protection against tumorigenesis 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 American Institute of Nutrition-93G diets made with casein (CAS), soy protein isolate (SPI) or CAS supplemented with genistein (GEN). Mammary glands of post-natal day (PND) 50 rats prior to NMU administration were examined for apoptotic status, pro-apoptotic gene expression and immunoreactive phosphatase and tensin homolog deleted on chromosome ten (PTEN) and epithelial cadherin (E-cadherin) levels, whereas mammary tumor parameters were evaluated 99 days post-NMU. Animals exposed only in utero to SPI had increased tumor latency, decreased tumor multiplicity and lower higher grade tumors, than those fed CAS. In utero exposure to GEN resulted in similar tumor parameters as the CAS group, whereas 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 terminal end bud apoptotic status and PTEN expression, than the other diet groups. Rats exposed only in utero to SPI or GEN had higher membrane E-cadherin in mammary structures than those lifetime-fed CAS or SPI. Thus, limited exposure during gestation to SPI can positively influence resistance to chemically induced mammary tumorigenesis later in life. Preventative strategies against mammary and other types of cancer might be uncovered by refinement of the developmental window for dietary factor exposure.
Abbreviations: CAS, casein; DCIS, ductal carcinoma in situ; DE, ductal epithelium; DMBA, 7,12-dimethylbenz(a)anthracene; E-cadherin, epithelial cadherin; GEN, genistein; IDC, invasive ductal carcinoma; NMU, N-methyl-N-nitrosourea; PND, post-natal day; PTEN, phosphatase and tensin homolog deleted on chromosome ten; SPI, soy protein isolate; TEB, terminal end bud
Received June 17, 2006; revised November 22, 2006; accepted November 27, 2006.
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