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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.12 P.1034-1044


ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells

Author(s):  Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN

Affiliation(s):  Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; more

Corresponding email(s):   litan@fudan.edu.cn

Key Words:  Apolipoprotein A-I (ApoA-I), Estrogen receptor α, (ERα, ), Acetylation of histone 3 lysine 27 (H3K27ac), p300, Breast cancer

Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN. ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells[J]. Journal of Zhejiang University Science B, 2021, 22(12): 1034-1044.

@article{title="ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells",
author="Bingjie WANG, Yinghui SHEN, Tianyu LIU, Li TAN",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells
%A Bingjie WANG
%A Yinghui SHEN
%A Tianyu LIU
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 12
%P 1034-1044
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100393

T1 - ERα promotes transcription of tumor suppressor gene ApoA-I by establishing H3K27ac-enriched chromatin microenvironment in breast cancer cells
A1 - Bingjie WANG
A1 - Yinghui SHEN
A1 - Tianyu LIU
A1 - Li TAN
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 12
SP - 1034
EP - 1044
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100393

)%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>apolipoprotein A-I (ApoA-I), the main protein component of high-density lipoprotein (HDL), plays a pivotal role in reverse cholesterol transport (RCT). Previous studies indicated a reduction of serum ApoA-I levels in various types of cancer, suggesting ApoA-I as a potential cancer biomarker. Herein, ectopically overexpressed ApoA-I in MDA-MB-231 breast cancer cells was observed to have antitumor effects, inhibiting cell proliferation and migration. Subsequent studies on the mechanism of expression regulation revealed that estradiol (E2)/estrogen receptor α; (ERα;) signaling activates ApoA-I gene transcription in breast cancer cells. Mechanistically, our ChIP-seq data showed that ERα directly binds to the estrogen response element (ERE) site within the ApoA-I gene and establishes an acetylation of histone 3 lysine 27 (H3K27ac)‍-enriched chromatin microenvironment. Conversely, Fulvestrant (ICI 182780) treatment blocked ERαbinding to ERE within the ApoA-I gene and downregulated the H3K27ac level on the ApoA-I gene. Treatment with p300 inhibitor also significantly decreased the ApoA-I messenger RNA (mRNA) level in MCF7 cells. Furthermore, the analysis of data from The Cancer Genome Atlas (TCGA) revealed a positive correlation between ERα and ApoA-I expression in breast cancer tissues. Taken together, our study not only revealed the antitumor potential of ApoA-I at the cellular level, but also found that ERα promotes the transcription of ApoA-I gene through direct genomic effects, and p300 may act as a co-activator of ERα in this process.




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[1]Aguirre-PortolésC, FeliuJ, RegleroG, et al., 2018. ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour growth and caveolin-1-dependent invasiveness, and these effects can be ameliorated using the BET inhibitor apabetalone. Mol Oncol, 12(10):1735-1752.

[2]AnzickSL, KononenJ, WalkerRL, et al., 1997. A1B1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science, 277(5328):965-968.

[3]BourdeauV, DeschênesJ, MétivierR, et al., 2004. Genome-wide identification of high-affinity estrogen response elements in human and mouse. Mol Endocrinol, 18(6):1411-1427.

[4]CedóL, García-LeónA, Baila-RuedaL, et al., 2016. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer. Sci Rep, 6:36387.

[5]ChenCL, LinTS, TsaiCH, et al., 2013. Identification of potential bladder cancer markers in urine by abundant-protein depletion coupled with quantitative proteomics. J Proteomics, 85:28-43.

[6]CirielloG, GatzaML, BeckAH, et al., 2015. Comprehensive molecular portraits of invasive lobular breast cancer. Cell, 163(2):506-519.

[7]CortesiL, BarchettiA, de MatteisE, et al., 2009. Identification of protein clusters predictive of response to chemotherapy in breast cancer patients. J Proteome Res, 8(11):4916-4933.

[8]GaoF, VasquezSX, SuF, et al., 2011. L-5F, an apolipoprotein A-I mimetic, inhibits tumor angiogenesis by suppressing VEGF/basic FGF signaling pathways. Integr Biol, 3(4):479-489.

[9]GaoF, ChattopadhyayA, NavabM, et al., 2012. Apolipoprotein A-I mimetic peptides inhibit expression and activity of hypoxia-inducible factor-1α in human ovarian cancer cell lines and a mouse ovarian cancer model. J Pharmacol Exp Ther, 342(2):255-262.

[10]GeorgilaK, VyrlaD, DrakosE, 2019. Apolipoprotein A-I (ApoA-I), immunity, inflammation and cancer. Cancers, 11(8):1097.

[11]GkouskouKK, IoannouM, PavlopoulosGA, et al., 2016. Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis. Oncogene, 35(19):2496-2505.

[12]GonçalvesA, EsterniB, BertucciF, et al., 2006. Postoperative serum proteomic profiles may predict metastatic relapse in high-risk primary breast cancer patients receiving adjuvant chemotherapy. Oncogene, 25(7):981-989.

[13]GordonSM, HofmannS, AskewDS, et al., 2011. High density lipoprotein: it's not just about lipid transport anymore. Trends Endocrinol Metab, 22(1):9-15.

[14]HalleyP, KadakkuzhaBM, FaghihiMA, et al., 2014. Regulation of the apolipoprotein gene cluster by a long noncoding RNA. Cell Rep, 6(1):222-230.

[15]HankerAB, SudhanDR, ArteagaCL, 2020. Overcoming endocrine resistance in breast cancer. Cancer Cell, 37(4):496-513.

[16]HeldringN, PikeA, AnderssonS, et al., 2007. Estrogen receptors: how do they signal and what are their targets. Physiol Rev, 87(3):905-931.

[17]HerynkMH, FuquaSAW, 2004. Estrogen receptor mutations in human disease. Endocr Rev, 25(6):869-898.

[18]KardassisD, MosialouI, KanakiM, et al., 2014. Metabolism of HDL and its regulation. Curr Med Chem, 21(25):2864-2880.

[19]KlingeCM, 2001. Estrogen receptor interaction with estrogen response elements. Nucleic Acids Res, 29(14):2905-2919.

[20]KongLC, TanL, LvRT, et al., 2016. A primary role of TET proteins in establishment and maintenance of De Novo bivalency at CpG islands. Nucleic Acids Res, 44(18):8682-8692.

[21]LevinER, PietrasRJ, 2008. Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res Treat, 108(3):351-361.

[22]LiWH, TanimuraM, LuoCC, et al., 1988. The apolipoprotein multigene family: biosynthesis, structure, structure‒function relationships, and evolution. J Lipid Res, 29(3):245-271.

[23]LiuL, ShenYH, ZhuXG, et al., 2018. ERα is a negative regulator of PD-L1 gene transcription in breast cancer. Biochem Biophys Res Commun, 505(1):157-161.

[24]MartinLJ, MelnichoukO, HusztiE, et al., 2015. Serum lipids, lipoproteins, and risk of breast cancer: a nested case-control study using multiple time points. J Nat Cancer Inst, 107(5):djv032.

[25]McMahonC, SuthiphongchaiT, DiRenzoJ, et al., 1999. P/CAF associates with cyclin D1 and potentiates its activation of the estrogen receptor. Proc Natl Acad Sci USA, 96(10):5382-5387.

[26]MussiP, LiaoL, ParkSE, et al., 2006. Haploinsufficiency of the corepressor of estrogen receptor activity (REA) enhances estrogen receptor function in the mammary gland. Proc Natl Acad Sci USA, 103(45):16716-16721.

[27]PengMY, ZhangQ, ChengYN, et al., 2017. Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression. Oncotarget, 8(59):99693-99706.

[28]ReddyST, NavabM, AnantharamaiahGM, et al., 2014. Apolipoprotein A-I mimetics. Curr Opin Lipidol, 25(4):304-308.

[29]ShaoBH, HeineckeJW, 2018. Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions? Expert Rev Proteomics, 15(1):31-40.

[30]ShiFY, WuH, QuK, et al., 2018. Identification of serum proteins AHSG, FGA and APOA-I as diagnostic biomarkers for gastric cancer. Clin Proteomics, 15:18.

[31]VrtačnikP, OstanekB, Mencej-BedračS, et al., 2014. The many faces of estrogen signaling. Biochem Med, 24(3):329-342.

[32]WaksAG, WinerEP, 2019. Breast cancer treatment: a review. JAMA, 321(3):288-300.

[33]XuBH, LiQ, ChenN, et al., 2019. The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells. Nucleic Acids Res, 47(5):2322-2335.

[34]Zamanian-DaryoushM, DidonatoJA, 2015. Apolipoprotein A-I and cancer. Front Pharmacol, 6:265.

[35]Zamanian-DaryoushM, LindnerD, TallantTC, et al., 2013. The cardioprotective protein apolipoprotein A1 promotes potent anti-tumorigenic effects. J Biol Chem, 288(29):21237-21252.

[36]ZhangJW, CaiY, HuHB, et al., 2016. Nomogram basing pre-treatment parameters predicting early response for locally advanced rectal cancer with neoadjuvant chemotherapy alone: a subgroup efficacy analysis of FOWARC study. Oncotarget, 7(4):5053-5062.

[37]ZografosE, AnagnostopoulosAK, PapadopoulouA, et al., 2019. Serum proteomic signatures of male breast cancer. Cancer Genomics Proteomics, 16(2):129-137.

[38]ZwijsenRML, BuckleRS, HijmansEM, et al., 1998. Ligand-independent recruitment of steroid receptor coactivators to estrogen receptor by cyclin D1. Genes Dev, 12(22):3488-3498.

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