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Study on mouse model of triple-negative breast cancer: association between higher parity and triple-negative breast cancer

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Abstract

To investigate the association between high parity and triple-negative breast cancer (TNBC), and explore the etiologic mechanisms of TNBC in Tientsin Albinao 2 (TA2) mice model. After the TA2 mice model with high parity and TNBC had been established, the cell proliferation and apoptosis were detected by immunohistochemical and TUNEL staining in mammary epithelia from different conditions, which included non-pregnancy, low and high gravidity in pregnancy, and carcinogenesis. Apoptotic signaling was analyzed by measuring bcl-2, bax, caspase-3, and caspase-9 expression using immunohistochemistry (IHC), western blot, and real-time PCR technique. Estrogen receptor α (ERα) and progesterone receptor (PR) were determined by immunohistochemical staining and real-time PCR. Both proliferation and apoptosis in mammary epithelia changed with the increasing of parity. Immunohistochemistry revealed increased cell proliferation and apoptosis were related with upregulation of ERα, PR, bcl-2, bax, caspase-3, and caspase-9 expression, especially during the fourth pregnancy. Mammary gland in the fourth pregnancy stage was the closest to precancerous. In precancerous mammary gland, cell proliferation rate was much higher than apoptosis rate. High parity could increase the ovarian hormones level and alter ovarian hormone receptor levels in TA2 mice, and their sensitivity to ovarian hormones result in the imbalance between cell proliferation and apoptosis in precancerous mammary epithelial cells.

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Acknowledgments

The authors thank the Department of Immunology, Tianjin Cancer Institute for their technical assistance. We also thank the Experimental Animal Center at Tianjin Medical University for providing experimental animals. This work was supported by a grant This work was supported by a grant from the National Natural Science Foundation of China (no. 81372467).

Conflict of interest

The authors declare there is no conflict of interest.

Author information

Authors and Affiliations

  1. Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Department of Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, 300060, People’s Republic of China

    Chun Huang

  2. Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Qi Xiang Tai Road 22#, Heping District, Tianjin, 300070, People’s Republic of China

    Xuan Wang

  3. Department of Pathology, Tianjin Cancer Institute and Hospital, Ti Yuan Bei, Huan Hu Xi Road, He Xi District, Tianjin, 300060, People’s Republic of China

    Xuan Wang, Baocun Sun, Yanfen Cui & Yan Li

  4. Department of Pathology, Tianjin Medical University, Tianjin, People’s Republic of China

    Baocun Sun & Xiulan Zhao

  5. Department of Digestive, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China

    Man Li

  6. Department of Pathology, Medical College of the Chinese People’s Armed Police Forces, Tianjin, People’s Republic of China

    Yanjun Gu

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  1. Chun Huang
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Corresponding authors

Correspondence to Xuan Wang or Baocun Sun.

Additional information

Chun Huang and Xuan Wang contributed equally.

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Huang, C., Wang, X., Sun, B. et al. Study on mouse model of triple-negative breast cancer: association between higher parity and triple-negative breast cancer. Targ Oncol 10, 85–97 (2015). https://doi.org/10.1007/s11523-014-0316-y

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  • DOI: https://doi.org/10.1007/s11523-014-0316-y

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