Inhibition of NMU-induced mammary tumorigenesis by dietary soy.
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.
Simmen
Rosalia C M
RC
Arkansas Children's Nutrition Center, Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. simmenrosalia@uams.edu
Eason
Renea R
RR
Till
S Reneé
SR
Chatman
Leon
L
Velarde
Michael C
MC
Geng
Yan
Y
Korourian
Sohelia
S
Badger
Thomas M
TM
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000517:prevention & control; D049109:Cell Proliferation; D018890:Chemoprevention; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D030262:Soybean Proteins / Q000494:pharmacology*
D000477:Alkylating Agents; D008770:Methylnitrosourea; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D030262:Soybean Proteins