The aim of this study was to extend our previous observations on the soy modulation of biochemical parameters in 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors, by simultaneously investigating the expression of estrogen receptor-alpha (ERalpha), estrogen receptor-beta (ERbeta), progesterone receptor (PR), apoptosis, neu, and markers of cell proliferation, such as proliferating cell nuclear antigen (PCNA) by immunohistochemistry. The percentage of ERalpha positive tumors was 65.8% in masses from control animals, and significantly dropped to 36.8% in tumors from soy treated rats (P=0.010). The percentage of ERbeta positive tumors was 70.3% in masses from control animals vs. 50.0% in tumors from soy exposed animals (P=0.066). Moreover, the percentage of cases which were both ERalpha and ERbeta positive was significantly lower (17.6%) in soy treated than in control animals (51.3%) (P=0.006). The percentage of PR positive tumors was 34.2% in control animals vs. 2.6% in tumors from soy treated rats (P=0.0006). There were no statistically significant differences in the percentage of tumors positively stained for neu, apoptosis, or PCNA, in control vs. soy treated rats. However, when analyzing the reciprocal correlation among the different biochemical parameters we showed that, in treated animals, the majority of ERalpha positive tumors (91.7%) were also PCNA positive (P=0.036). The median percentage of PCNA positivity was significantly higher in ERalpha positive than in ERalpha negative tumors (25 vs. 5%) (P=0.0031). Moreover, an association was found between PCNA and neu status since all neu positive tumors were also PCNA positive (P=0.011).
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