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Activation of mitochondrial unfolded protein response is associated with Her2-overexpression breast cancer

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Mitochondrial unfolding protein are abundant in breast cancer cells, but the mechanism by which breast cancer cells resist apoptosis is still not fully elucidated. In this study, we explored the role of mitochondrial unfolded protein response (mtUPR)-related proteins in four types of breast cancer tissues.

Methods

Mitochondrial fractions were taken from four breast cancer tissues (luminal A, luminal B, Her2 –overexpression, and TNBC) and the expression of mitochondrial polyubiquitinated proteins was observed by western blot and ELISA. In addition, the expression of hsp10, hsp60, and clpp in mitochondria was observed by western blot in breast cancer tissues and adjacent tissues, and confirmed by ELISA. The expression levels of hsp10 and hsp60 were correlated with clinicopathological parameters in 114 breast cancer patients.

Results

We found an increase in the performance of mitochondrial polyubiquitinated proteins in breast cancer tissues of luminal A, luminal B, Her2-overexpression, and TNBC. The mitochondrial hsp10, hsp60, and clpp are abundantly expressed in breast cancer tissues rather than adjacent noncancerous tissues. The expression levels of mitochondrial hsp10 and hsp60 were highest in histological grade 3 breast cancer tissues. Additionally, mitochondria with high hsp60 expression were more present in Her2-positive tumors.

Conclusions

We observed that mtUPR was specifically activated in breast cancer tissues but inactivated in normal mammary tissue. MtUPR had also exhibited a particular increase in Her2-overexpression tumors but not in ER- or PR-positive tumors. Taken together, we suggested that mtUPR may act as a potential candidate for developing novel Her2-overexpression breast cancer therapy.

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Acknowledgements

We would like to thank Dr. Pei-Shan Ho from the Department of Oral Hygiene of Kaohsiung Medical University for the data analysis. The experiments were performed using General Laboratory in Kaohsiung Municipal Ta-Tung Hospital. This work was supported by grants from the Kaohsiung Municipal Ta-Tung Hospital (kmtth-103-008, kmtth-103-042, KMU-DK109004 ~ 1), Ministry Science and Technology (MOST 105-2314-B-037-039-MY3) and Kaohsiung Medical University (KMU-TC108A03).

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Authors and Affiliations

  1. Division of Breast Surgery, Department of Surgery, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC

    Fang-Ming Chen, Fu Ou-Yang, Jung-Yu Kan, Li-Chun Kao & Ming-Feng Hou

  2. Department of Surgery, Kaohsiung Municipal Ta-Tung Hospital, No. 68, Zhonghua 3rd Rd., Qianjin Dist., Kaohsiung, 801, Taiwan, ROC

    Fang-Ming Chen, Fu Ou-Yang, Jung-Yu Kan, Li-Chun Kao & Ming-Feng Hou

  3. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC

    Fang-Ming Chen & Ming-Feng Hou

  4. Drug Development and Value Creation Research Center, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, 807, Taiwan, ROC

    Fang-Ming Chen & Ming-Feng Hou

  5. Center of Teaching and Research, Kaohsiung Municipal Ta‐Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC

    Li-Ju Huang

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  1. Fang-Ming Chen
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Correspondence to Ming-Feng Hou.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Kaohsiung Medical University Hospital [KMUHIRB-F(II)-20150031] and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Chen, FM., Huang, LJ., Ou-Yang, F. et al. Activation of mitochondrial unfolded protein response is associated with Her2-overexpression breast cancer. Breast Cancer Res Treat 183, 61–70 (2020). https://doi.org/10.1007/s10549-020-05729-9

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  • DOI: https://doi.org/10.1007/s10549-020-05729-9

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