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    Please use this identifier to cite or link to this item: http://asiair.asia.edu.tw/ir/handle/310904400/112750


    Title: Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation
    Authors: Thanh, Kieu H;Huynh, Thanh Kieu;Ho, Chien-Yi;Ho, Chien-Yi;Tsai, Chi-Hua;Tsai, Chi-Hua;王建國;Wang, Chien-Kuo
    Contributors: 醫學檢驗暨生物技術學系
    Keywords: ErbB family;and HSP90;breast cancer;lysosome;proteasome.
    Date: 2019-09
    Issue Date: 2020-08-27 15:21:21 (UTC+8)
    Publisher: 亞洲大學
    Abstract: Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.
    Relation: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
    Appears in Collections:[醫學檢驗暨生物技術學系] 期刊論文

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