Rats Models Of Premalignant Breast Disease

【Objective】:Breast cancer is a malignant tumor that endengering women's health seriously and have become the first cause of women's death in the Western developed countries.Putting forward "a multi-stage breast cancer model" on the end of the century,pointing out that the transformation from normal mammary epithelial cells to malignant experienced the gradual process of hyperplasia to atypical hyperplasia to carcinoma in situ to invasive carcinoma.In the development prior to becoming invasive carcinomas,atypical hyperplasia and carcinoma in situ may be a very long time at a relatively steady state,which is called precancerous lesions of breast cancer.It includes part without or with atypical hyperplasia hyperplastic breast disease,intraductal papilloma, sclerosing adenosis,ductal carcinoma in situ and lobular carcinoma in situand so on.Premalignant breast disease is a set of both morphological and genetic changes diseases,which must happened in stages and a prelude to malignant,and in the process of prior to malignant are reversible. Therefore,the basic research and the level of diagnosis and treatment of premalignant breast disease has a great significance of breast cancer prevention and control.With the rapid increase in morbidity trends,in order to control the threat of breast cancer,the treatment requires not only a reasonable strategy,but also the need for effective preventive measures.Currently, Europe and the United States in the clinical strategy in breast cancer chemoprevention of breast cancer have a significant impact on prevention and treatment.Study of precancerous lesions can not only explore the pathogenesis of breast cancer,but also its mechanism is more the importance of vesting.In view of the occurrence of breast cancer is a long-term progressive pathological process,based on the difficulty of the existence of a number of factors,it is difficult to observe in the human itself,so the establishment of a suitable animal model can replace the human studies to carry out in order to provide a good research subjects and materials,so as to provide experimental basis for the prevention of premalignancy of breast cancer's transfer mechanism and have a great value.At present,the establishment of breast hyperplasia and breast cancer animal model are mature,it is regrettable that model of precancerous lesions are little to success for difficult to determine the end of experiment,if the end of the experiment is too late,then the majority of models developed into breast cancer,if the premature end of the experiment,the majority of models are still in the proliferative stage, resulting in a lower success rate.With the progress of the study of molecular biology,a number of process-related biomarkers has been found in benign breast disease or precancerous diseases,the results show that the regulation of cell proliferation biomarkers have already significant changed in the period of precancerous lesions.In which ER,PR,CerbB-2,Ki67,COX-2,TGF-β1 have been proved playing an important role in the course of regulation of breast cell proliferation and has been validated have a great significance in the process of epithelial cells Carcinogenesis both at home and abroad.Some precancerous lesions of breast have the same molecular changes with invasive carcinomas.Establishment animal models of premalignant breast disease and research on ER,PR,CerbB-2,Ki67, COX-2,TGF-β1 in premalignant breast disease,may provide a research base which could explore in depth the causes and mechanism of pathogenesis, To provide credible and viable basis for achieving the preventive effect.【Methods】:30 SD ratswere randomly divided into 4 groups,GroupⅠ:blank control 6;GroupⅡ:DMBA +hormone sequential 5 days 8;GroupⅢ:DMBA +hormone sequential 30 days 8;GroupⅣ:DMBA only 8.The general morphology,pathology and immunohistochemieal expression of ER,PR,CerbB-2,Ki67,COX-2,TGF-β1 were observed When the rats were executed after 60 days.【Results】:The incidence of premalignant breast disease in groupⅡ(66.67%) was significantly higher than groupⅠ(0%),groupⅢ(42.86%) and groupⅣ(28.57%)(P＜0.01).Immunohistochemistry results showed that the expression of ERα,Ki67,COX-2,TGF-β1 in groupⅡ,groupⅢand groupⅣhas statistical significance to groupⅠ(P＜0.01) and have a higher positive score,groupⅡ,groupⅢand groupⅣhas not statistical significance(P＞0.05);Erβin groupⅡ,groupⅢand groupⅣhas statistical significance to groupⅠ(P＜0.01) and have a low positive score,groupⅡ,groupⅢand groupⅣhas not statistical significance (P＞0.05).PR,CerbB-2 in groupⅠ,groupⅡ,groupⅢand groupⅣcomparison of each group were not statistically significant(P＞0.05).【Conclusion:】:The result suggest DMBA+hormone sequential 5 days method is the best way to establish rat models of breast disease;The incidence of ERα,Ki67,COX-2,TGF-β1 in premalignant breast disease were significantly higher than the groupⅠ,ERβwas slightly lower than the groupⅠ,ERα,ERβ,Ki67,COX-2,TGFβ1 immunohistochemistry five indicators in groupⅡhas the roughly same with the groupⅢand groupⅣ.PR,CerbB-2,in premalignant breast disease has not changed significantly and to be further explored.