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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #187614
Title: ENHANCED PROGESTERONE RECEPTOR A EXPRESSION BY DIETARY SOY IN A HORMONE-DEPENDENT (NMU) MODEL OF RAT MAMMARY CARCINOGENESIS: IMPLICATIONS FOR TUMOR PROGRESSION

Author
item DAVE, BHUVANESH - ACNC/UAMS
item EASON, RENEA - ACNC
item TILL, RENEE - ACNC
item KOROURIAN, SOHEILA - UAMS
item SIMMEN, ROSALIA - ACNC/UAMS

Submitted to: American Association of Cancer Research
Publication Type: Abstract Only
Publication Acceptance Date: 2/6/2006
Publication Date: 3/27/2006
Citation: Dave, B., Eason, R., Till, R.S., Korourian, S., Simmen, R.C. 2006. Enhanced progesterone receptor a expression by dietary soy in a hormone-dependent (NMU) model of rat mammary carcinogenesis: implications for tumor progression [abstract]. Proceedings of the American Association of Cancer Research. 47:5582.

Interpretive Summary: Our lab has previously shown that rats fed lifetime diet of soy proteins as the sole protein source are protected against breast cancer. However, pathological examination of the tumors of these rats showed that soy-fed rats had more invasive tumors than the rats fed the control casein diet. After sacrificing the tumored rats we collected the blood for progesterone level analysis and found that soy fed rats had a lower level of serum progesterone. We followed this lead by looking at the Progesterone receptor A(PR-A) and B (PR-B) levels in the mammary glands without tumor development and with tumor development and found an increase in the Progesterone receptor A expression in comparison to Progesterone receptor B. Upon further investigation we also found that the oncogene Her-2-Neu, which is known to cause more invasive breast cancers was increased in the mammary glands of these animals. Since cancer patients with mammary PR-A do not respond well to endocrine therapy, our findings of increased PRA levels in rats fed dietary soy have important implications for women with breast cancer.

Technical Abstract: In previous work, we showed that lifetime exposure of Sprague-Dawley rats to AIN-93G diet made with soy protein isolate (SPI) as sole protein source, protected against NMU-induced mammary tumorigenesis, relative to the control (Casein, CAS) diet. The reduction in mammary tumor incidence (by 20%) with dietary SPI mimics the low breast cancer incidence in women with high dietary intake of soy foods. Interestingly, in SPI-fed rats that developed mammary tumors, a higher percentage of tumors with infiltrating ductal carcinoma (IDC) than ductal carcinoma in situ (DCIS) was observed, when compared to tumors of the CAS group, suggesting potential effects of soy components on tumor progression. Given the reported inverse correlation between serum progesterone (P) levels and breast cancer risk in premenopausal women; the increased progesterone receptor (PR) expression in mammary tissue of women consuming dietary soy supplement; and the decreased P levels in women on soy-based diets, we evaluated the expression of PR-A and PR-B isoforms in pathologically normal (designated normal) mammary glands and corresponding mammary tumors (IDC+DCIS), and serum P levels of NMU-exposed rats fed CAS or SPI. Transcript levels for PR-A were higher in normal mammary glands for the SPI than for the CAS group, while those for PR-B did not differ with diet. The ratio of PR-A/PR-B was four-fold higher for the SPI relative to the CAS group in normal mammary glands, but was not different in tumor tissues. The increased PR-A/PR-B ratio with SPI was accompanied by increased levels of HER-2/neu oncogene, whose up-regulated expression is reported in invasive breast cancers. Antibody against PR-A/B proteins demonstrated nuclear PR expression in normal mammary glands and mammary tumors, while antibody specific to PR-B showed negligible expression of this PR isoform. Serum P levels were lower (P<0.01) in tumor-bearing rats fed SPI than those fed CAS, with no differences (P=0.259) noted for serum estrogen. Since breast cancer patients with mammary PR-A greater than PR-B expression were found to be less responsive to endocrine therapy than those with higher PR-B expression, our findings of increased expression of PR-A with dietary soy in rats with NMU-induced tumors may have important implications for women with benign or malignant breast cancer consuming soy-based diets.