| Objiective:In this study we examined the effect of soybean isoflavones on initiation and progression of breast cancer of MMTV-erbB-2 transgenic female mice in different age,and investigated the underlying mechanisms.Methods:120 MMTV-erbB-2 transgenic female mice were selected and divided into four groups:early intervention group,advanced intervention group,full intervention group and control group.We respectively treated with soybean feed from week 4 to week 12,week 20 to week 60,week 4 to week 60 and the control group treated with contrast feed form week 4 to week 60.To observe the growth and development,the body weight,the tumor incidence,the tumor latent period,tumor location and tumor growth rate of breast cancer. Mammary gland morphology at age 10 week was analyzed by whole mount. And used immunohistochemistry SP method detected expression of erbB-2 in 10 weeks of breast tissue.Mammary gland morphology was analyzed by HE staining.To investigate the underlying mechanisms,the signal transduction in ERK1,ERK2 and c-Fos pathways of breast cancer tissue and natural breast tissue was examined using Immunohistochemistry.Results:We found that the weight of early intervention group and full intervention group increase slower than advanced intervention group and control group(P<0.05).Compared with the control diet group mice, the TEB structure count of groups intervented by soy isoflavones significantly decreased(P<0.05).The expression of erbB-2 protein among the different groups was not statistically significant(P>0.05). Tumor location in four groups almost was the three pair of mammary gland;And the rate of tumor growth has no significant difference in four groups (P>0.05).Morphology analysis of HE staining showed that ductal carcinoma in situ in 13 cases,invasive ductal carcinoma in 46 cases,invasive lobular carcinoma in 8 cases,atypical hyperplasia in 4 cases,lung metastasis in 1 case.The incidence of early intervention group,advanced intervention group,full intervention group and the control group were:48%,28%,20% and 92%.Compared with the control group,the other three groups were decreased significantly (P<0.01).. The latent period were (47.67±9.25)weeks,(47.29±14.13)weeks,(51.8±6.69)weeks and(49.91±8.07)weeks. There was no significant difference in the latent period of breast cancer (P>0.05). And IHC indicated that the positive rates of ERK1, ERK2 and c-Fos in breast cancer tissue was 71.6%),68.7% and 61.2% respectively,while the positive rates of these proteins in benignant mammary tissue was 27.7%,19.1% and 12.8% respectively(P<0.01).Compared with the control group,the positive rates of these proteins in breast cancer tissue in the other three groups has no significance(P>0.05).Conclusion:ErbB-2 transgenic mice have good capability of propagation and carry erbB-2 gene adaptation.The morphological development of mouse mammary gland of MMTV-erbB-2 transgenic mice intervented by soybean isoflavones have a certain change. Soy isoflavones may have a preventive effect on the initiation of breast cancer. This have a great guiding significance to the early prevention of breast cancer. There was no correlation between the expression of ERK1/2, c-Fos and the inhibition of soy isoflavones to MMTV-erbB-2 transgenic mice. The signal path must be investigated. |
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