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

• Published in: Breast cancer research and treatment Vol. 183; no. 1; pp. 61 - 70
• Main Authors: Chen, Fang-Ming, Huang, Li-Ju, Ou-Yang, Fu, Kan, Jung-Yu, Kao, Li-Chun, Hou, Ming-Feng
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2020; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Apoptosis; Blotting, Western; Breast cancer; Breast Neoplasms - metabolism; Cancer research; Chaperonin 10 - biosynthesis; Chaperonin 10 - genetics; Chaperonin 60 - biosynthesis; Chaperonin 60 - genetics; Endopeptidase Clp - biosynthesis; Endopeptidase Clp - genetics; Enzyme-Linked Immunosorbent Assay; ErbB-2 protein; Ethylenediaminetetraacetic acid; Female; Gene Expression Regulation, Neoplastic; Health aspects; Heat shock proteins; Hsp60 protein; Humans; Medical colleges; Medicine; Medicine & Public Health; Middle Aged; Mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - biosynthesis; Mitochondrial Proteins - genetics; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oncology; Preclinical Study; Protein folding; Proteins; Receptor, ErbB-2 - biosynthesis; Receptor, ErbB-2 - genetics; Triple Negative Breast Neoplasms - metabolism; Tumors; Unfolded Protein Response; Breast cancer‧mitochondrial unfolded protein response; mtUPR; Her2-overexpression
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-020-05729-9

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.