Inhibition of NMU-induced mammary tumorigenesis by dietary soy

Simmen, Rosalia C.M.; Eason, Renea R.; Till, S. Reneé; Chatman, Leon; Velarde, Michael C.; Geng, Yan; Korourian, Sohelia; Badger, Thomas M.

doi:10.1016/j.canlet.2004.11.009

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Volume 224, Issue 1 , Pages 45-52, 16 June 2005

Inhibition of NMU-induced mammary tumorigenesis by dietary soy☆

Rosalia C.M. Simmen
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Corresponding author. Address: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences and Arkansas Children's Nutrition Center, Little Rock, AR, USA. Tel.: +1 501 364 2849; fax: +1 501 364 3161.
Renea R. Eason
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
S. Reneé Till
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Leon Chatman Jr.
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Michael C. Velarde
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Yan Geng
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Sohelia Korourian
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA
Thomas M. Badger
- Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR, USA
- Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA

Received 4 October 2004; received in revised form 30 October 2004; accepted 1 November 2004.

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, tumored SPI⁺ rats had lower serum progesterone levels than those fed CAS, while serum estrogen did not differ. Serum from tumored 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.

Keywords: Mammary carcinoma, NMU, Soy proteins, Apoptosis, Progesterone