气候变化领域集成服务门户(CCPortal): Drivers and suppressors of triple-negative breast cancer

CCPortal

DOI	10.1073/pnas.2104162118
	Drivers and suppressors of triple-negative breast cancer
	Wu W.; Warner M.; Wang L.; He W.-W.; Zhao R.; Guan X.; Botero C.; Huang B.; Ion C.; Coombes C.; Gustafsson J.-A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	To identify regulators of triple-negative breast cancer (TNBC), gene expression profiles of malignant parts of TNBC (mTNBC) and normal adjacent (nadj) parts of the same breasts have been compared. We are interested in the roles of estrogen receptor β (ERβ) and the cytochrome P450 family (CYPs) as drivers of TNBC. We examined by RNA sequencing the mTNBC and nadj parts of five women. We found more than a fivefold elevation in mTNBC of genes already known to be expressed in TNBC: BIRC5/survivin, Wnt-10A and -7B, matrix metalloproteinases (MMPs), chemokines, anterior gradient proteins, and lysophosphatidic acid receptor and the known basal characteristics of TNBC, sox10, ROPN1B, and Col9a3. There were two unexpected findings: 1) a strong induction of CYPs involved in activation of fatty acids (CYP4), and in inactivation of calcitriol (CYP24A1) and retinoic acid (CYP26A1); and 2) a marked down-regulation of FOS, FRA1, and JUN, known tethering partners of ERβ. ERβ is expressed in 20 to 30% of TNBCs and is being evaluated as a target for treating TNBC. We used ERβ+ TNBC patient-derived xenografts in mice and found that the ERβ agonist LY500703 had no effect on growth or proliferation. Expression of CYPs was confirmed by immunohistochemistry in formalin-fixed and paraffin-embedded (FFPE) TNBC. In TNBC cell lines, the CYP4Z1-catalyzed fatty acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) increased proliferation, while calcitriol decreased proliferation but only after inhibition of CYP24A1. We conclude that CYP-mediated pathways can be drivers of TNBC but that ERβ is unlikely to be a tumor suppressor because the absence of its main tethering partners renders ERβ functionless on genes involved in proliferation and inflammation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Breast cancer; Cytochrome P450; Estrogen receptor beta; Fatty acid oxidation
语种	英语
scopus关键词	20 hydroxyicosatetraenoic acid; calcitriol; colecalciferol 24 hydroxylase; collagen type 9; cytochrome P450; cytochrome P450 family 4; estrogen receptor beta; matrix metalloproteinase; protein fos; retinoic acid; transcription factor Fra 1; transcription factor Sox10; Wnt10a protein; Wnt7b protein; amphibian protein; baculoviral IAP repeat containing protein 5; benzopyran derivative; BIRC5 protein, human; calcitriol; cytochrome P450; erteberel; estrogen receptor alpha; estrogen receptor beta; fatty acid; retinoic acid; transcriptome; Wnt protein; Wnt-10a protein, Pleurodeles waltl; animal experiment; animal model; animal tissue; Article; breast cancer cell line; cell proliferation; controlled study; down regulation; fatty acid oxidation; gene; gene expression profiling; human; human cell; human tissue; immunohistochemistry; mouse; nonhuman; paraffin embedding; protein expression; RNA sequencing; triple negative breast cancer; tumor xenograft; animal; drug effect; experimental neoplasm; female; gene expression regulation; genetics; metabolism; physiology; randomization; triple negative breast cancer; Amphibian Proteins; Animals; Benzopyrans; Calcitriol; Cytochrome P-450 Enzyme System; Down-Regulation; Estrogen Receptor alpha; Estrogen Receptor beta; Fatty Acids; Female; Gene Expression Regulation, Neoplastic; Humans; Mice; Neoplasms, Experimental; Random Allocation; Survivin; Transcriptome; Tretinoin; Triple Negative Breast Neoplasms; Wnt Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251060
作者单位	Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, United States; Department of Oncology, Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210000, China; Department of Thyroid and Breast Surgery, Affiliated Huaian No. 1 People's Hospital, Nanjing Medical University, Huaian, 223300, China; Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, W12 0NN, United Kingdom; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, SE-14186, Sweden
推荐引用方式 GB/T 7714	Wu W.,Warner M.,Wang L.,et al. Drivers and suppressors of triple-negative breast cancer[J],2021,118(33).
APA	Wu W..,Warner M..,Wang L..,He W.-W..,Zhao R..,...&Gustafsson J.-A..(2021).Drivers and suppressors of triple-negative breast cancer.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Wu W.,et al."Drivers and suppressors of triple-negative breast cancer".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).