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    標題: ABCB1 Regulates Immune Genes in Breast Cancer
    作者: Chen, Han -Kun
    Chen, Yi -Ling
    Wang, Chih-Yang
    Chung, Wei -Pang
    Fang, Jung -Hua
    Lai, Ming-Derg
    Hsu, Hui-Ping
    貢獻者: Chi Mei Med Ctr, Dept Surg
    Chia Nan Univ Pharm & Sci, Dept Hlth & Nutr
    Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Mol Biol & Drug Discovery
    Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Coll Med Sci & Technol
    Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Oncol
    Natl Cheng Kung Univ, Ctr Appl Nanomed
    Natl Cheng Kung Univ, Coll Med, Lab Anim Ctr
    Natl Cheng Kung Univ, Dept Biochem & Mol Biol
    Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med
    Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg
    Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg
    關鍵字: breast cancer
    ABC transporters
    ABCB1
    myeloid-derived suppressor cells
    patient-derived xenograft
    日期: 2023
    上傳時間: 2024-12-25 11:05:24 (UTC+8)
    出版者: DOVE MEDICAL PRESS LTD
    摘要: Background: Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and immune genes in breast cancer has not been widely studied.Methods: Microarray and RNA sequencing data were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal and Gene Expression Omnibus database. A patient-derived xenograft (PDX) model of HER2+ breast cancer was established to investigate the association between ABCB1 and immune genes in breast cancer.Results: Expression of ABCB1 increased in doxorubicin-selected MCF-7/ADR cells. High expression of ABCB1 mRNA is correlated with lymph-node metastasis and worse overall survival in patients with breast cancer. ABCB1 is positively correlated with IL6, CSF1, CSF3, and PTGS2. In the HER2+ stage IIA breast cancer PDX model, both doxorubicin and paclitaxel suppressed growth of P2 tumors. IL6, CSF1, CSF3, and PTGS2 expression were suppressed by paclitaxel but not doxorubicin. Intrasplenic MDSCs, including CD11b+Ly6G+ and CD11b+Ly6C+ cells, were more abundant than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well controlled after paclitaxel-trastuzumab combined therapy.Conclusion: ABCB1 was a poor predictor of HER2+ LN- breast cancer. Regulation of immune genes by ABCB1 contributed to cancer recurrence and treatment effect. The PDX model was suitable for investigation the expression of target genes and expansion of immune cells.
    關聯: Breast Cancer-Targets and Therapy, v.15, pp.801-811
    顯示於類別:[保健營養系(所) ] 期刊論文

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