| Nowadays, breast cancer as one of the most common and high death rate malignant tumor to women, had received widespread attention. Endoplasmic reticulum stress apoptosis pathway as the latest discovered apoptotic pathways, it is necessary to understand the changes of the related factors of the new pathway, we must to comprehend its mechanism and the relationship between each other, then we can predict new targets for clinical breast cancer detection and treatment.In this paper, SD rat model of spontaneous mammary gland tumors was utilized, On the basis of the pathology analysis to mammary gland, combined with the protein expression and mRNA expression of endoplasmic reticulum stress mediated apoptosis pathway related factors, to research the expression of the factors on the spontaneous breast tumor, then analyze the role of these factors on spontaneous breast tumor.130 (half male and female) 3-4-week-old SPF SD rats were used to build spontaneous mammary gland tumors model, and dissectted after feeding 60 weeks, colleted some naked eye not seen diseased breast tissues and the all mammary gland tissues that had abnormal lump, then fixed and saved the tissues with 4% paraformaldehyde and liquid nitrogen respectively. Completed H.E staining to observe the pathological changes, immunohistochemistry and fluorescence quantitative PCR test, which to research respectively from the pathological changes^ the expression level and distribution of protein and the mRNA expression levels of Calpain-2、GRP78、 Bax、 JNK、 Caspase-3. Caspase-12、CHC、Bcl-2.Results are as follows:the gross anatomy and pathology observations showed that male rats in the experiment did not see the occurrence of breast tumor, while the female occurrence rate of tumors was 21.54%(14/65), of which the occurrence rate of breast fibroadenoma was 10.77%(7/65), adenocarcinoma and papillary’carcinoma and invasive ductal carcinoma respectively was 4.62%(3/65),3.08%(2/65) and 3.08%(2/65). Immunohistochemistry’result showed:the protein expression of Calpain-2、CHOP、JNK、Caspas-12、Caspase-3 and Bax in the benign and malignant groups were declining compared to the corresponding control group, except Calpain-2 (P＜0.05) and JNK (P>0.05) in the comparison of the benign group and control group, the rest of the changes were very significant (P<0.01), and the expression of theses six factors in malignant group is lower than the benign group (P＜0.01). Instead, the expression of GRP78 and Bcl-2 in the experimental group compared with the control group were significantly increased, and the differences between benign and malignant were obvious (P＜0.01). According to the correlation analysis between Immunohistochemistry and RT-PCR, we can see that the expression of each factor were consistent between protein level and mRNA level. The correlation analysis between each factor’s protein and the changes of mRNA and the degree of tissue pathological changes showed:the Bax、CHOP、Caspase-12 and Caspase-3 had the most correlation to the degree of mammary tissue pathological changes.Based on the analysis of above results show that the occurrence of rats spontaneous breast tumor is closely related to gender, may also has a connection with breeding cycle, and the incidence of benign tumors and malignant tumors in females are the same, but benign breas tumor is fiber adenoma, while malignant tumor in pathological type diversity. The apoptosis pathway mediated by endoplasmic reticulum stress involve in the occurrence of the SD rat spontaneous mammary gland tumor, the protein expression and the mRNA expression level are consistent with each other. Especially the changes of Bax、CHOP、Caspase-12 and Caspase-3 are particularly significant, which suggest us this four factors may provide a direction for the early diagnosis and targeted treatment in clinical breast cancer. |
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