ABCB1 Regulates Immune Genes in Breast Cancer

doi:10.2147/BCTT.S421213

CNU IR > Pharmacy and Science > Dept. of Health and Nutrition (including master's program) > Periodical Articles > Item 310902800/34905

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34905

Title:	ABCB1 Regulates Immune Genes in Breast Cancer
Authors:	Chen, Han -Kun Chen, Yi -Ling Wang, Chih-Yang Chung, Wei -Pang Fang, Jung -Hua Lai, Ming-Derg Hsu, Hui-Ping
Contributors:	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
Keywords:	breast cancer ABC transporters ABCB1 myeloid-derived suppressor cells patient-derived xenograft
Date:	2023
Issue Date:	2024-12-25 11:05:24 (UTC+8)
Publisher:	DOVE MEDICAL PRESS LTD
Abstract:	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.
Relation:	Breast Cancer-Targets and Therapy, v.15, pp.801-811
Appears in Collections:	[Dept. of Health and Nutrition (including master's program)] Periodical Articles

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