TRIM24在乳腺癌内分泌治疗耐药中的作用及机制研究

doi:10.11904/j.issn.1002-3070.2024.06.008

Abstract

Abstract: Objective The aim of this study was to investigate the regulatory role and mechanism of TRIM24 in endocrine therapy resistance of breast cancer. Methods The relationship between TRIM24 expression and prognosis in breast cancer patients receiving endocrine therapy was analyzed by the Kaplan-Meier Plotter database.After treatment of breast cancer MCF7 cells or T47D cells with tamoxifen(TAM),the expression of TRIM24 was detected by qRT-PCR and Western blot.After knocking out TRIM24 in TAM sensitive MCF7/S0.5 cells and resistant cells MCF7/TAMR-1 cells,cell proliferation was measured by CCK 8 assay.After knocking out the estrogen receptor(ER)or treating with the selective progesterone receptor(PR)antagonist UPA(Ulipristal acetate)in MCF7 cells,the expression of TRIM24 was measured by qRT-PCR and Western blot.After PR was overexpressed in MCF7 cells,the expression of TRIM24 was detected by Western blot.The expression of human epidermal growth factor receptor 2(HER2)was detected by qRT PCR and Western blot after the overexpression of TRIM24. Results Among breast cancer patients receiving endocrine therapy,patients with high expression of TRIM24 had a shorter recurrence free survival(RFS)(P=0.027).TAM treatment could induce an increase of TRIM24 expression(P＜0.001);Knocking out TRIM24 significantly inhibited the proliferation of drug-resistant MCF7/TAMR-1 cells(P＜0.001),but had no effect on sensitive MCF7/S0.5 cells;After knocking out ER or treatment of PR antagonist,the expression of TRIM24 could be upregulated in MCF7 cells(P＜0.01),while overexpression of PR could down-regulate the expression of TRIM24.TRIM24 could activate the expression of HER2(P＜0.05). Conclusion PR negatively regulation of TRIM24 plays an important role in endocrine therapy resistance of breast cancer.

Key words: TRIM24, Tamoxifen, Progesterone receptor, Endocrine therapy resistance

CLC Number:

R737.9

PANG Wanying, AN Jing, LIU Zhaoliang. The role and mechanism of TRIM24 in endocrine therapy resistance of breast cancer[J]. Journal of Practical Oncology, 2024, 38(6): 402-409.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/10.11904/j.issn.1002-3070.2024.06.008

http://journal09.magtechjournal.com/Jwk3_syzlxzz/EN/Y2024/V38/I6/402

References

1 Bray F,Laversanne M,Sung H,et al.Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2024,74(3):229-263.
2 Nolan E,Lindeman GJ,Visvader JE.Deciphering breast cancer:from biology to the clinic[J].Cell,2023,186(8):1708-1728.
3 Burstein HJ.Systemic therapy for estrogen receptor-positive,HER2-negative breast cancer[J].N Engl J Med,2020,383(26):2557-2570.
4 Ali S,Rasool M,Chaoudhry H,et al.Molecular mechanisms and mode of tamoxifen resistance in breast cancer[J].Bioinformation,2016,12(3):135-139.
5 Ferrando L,Vingiani A,Garuti A,et al.ESR1 gene amplification and MAP3K mutations are selected during adjuvant endocrine therapies in relapsing hormone receptor-positive,HER2-negative breast cancer(HR+ HER2-BC)[J].PLoS Genet,2023,19(1):e1010563.
6 Nayar U,Cohen O,Kapstad C,et al.Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor-directed therapies[J].Nat Genet,2019,51(2):207-216.
7 Li H,Prever L,Hirsch E,et al.Targeting PI3K/AKT/mTOR signaling pathway in breast cancer[J].Cancers(Basel),2021,13(14):3517.
8 Garcia-Martinez L,Zhang Y,Nakata Y,et al.Epigenetic mechanisms in breast cancer therapy and resistance[J].Nat Commun,2021,12(1):1786.
9 Yu S,Wu R,Si Y,et al.Alternative splicing of ALDOA confers tamoxifen resistance in breast cancer[J].Oncogene,2024,43(39):2901-2913.
10 Yuan J,Yang L,Li Z,et al.The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer[J].Front Endocrinol(Lausanne),2023,14:1261283.
11 Miao ZF,Wang ZN,Zhao TT,et al.TRIM24 is upregulated in human gastric cancer and promotes gastric cancer cell growth and chemoresistance[J].Virchows Arch,2015,466(5):525-532.
12 Zhang L,Chen H,Ding B,et al.High expression of TRIM24 predicts worse prognosis and promotes proliferation and metastasis of epithelial ovarian cancer[J].J Ovarian Res,2022,15(1):19.
13 Zhang LH,Yin AA,Cheng JX,et al.TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway[J].Oncogene,2015,34(5):600-610.
14 Ma L,Yuan L,An J,et.al.Histone H3 lysine 23 acetylation is associated with oncogene TRIM24 expression and a poor prognosis in breast cancer[J].Tumor Biol,2016,37(11):14803-14812.
15 Shah VV,Duncan AD,Jiang S,et al.Mammary-specific expression of Trim24 establishes a mouse model of human metaplastic breast cancer[J].Nat Commun,2021,12(1):5389.
16 Sanjana NE,Shalem O,Zhang F.Improved vectors and genome-wide libraries for CRISPR screening[J].Nat Methods,2014,11(8):783-784.
17 Sahai V,Redig AJ,Collier KA,et al.Targeting BET bromodomain proteins in solid tumors[J].Oncotarget,2016,7(33):53997-54009.
18 Xu Y,Vakoc CR.Targeting cancer cells with BET bromodomain inhibitors[J].Cold Spring Harb Perspect Med,2017,7(7):26674.
19 Lv D,Li Y,Zhang W,et al.TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma[J].Nat Commun,2017,8(1):1454.
20 Xiang Q,Luo G,Zhang C,et al.Discovery,optimization and evaluation of 1-(indolin-1-yl)ethan-1-ones as novel selective TRIM24/BRPF1 bromodomain inhibitors[J].Eur J Med Chem,2022,236:114311.
21 Zhu Y,Zhao L,Shi K,et al.TRIM24 promotes hepatocellular carcinoma progression via AMPK signaling[J].Exp Cell Res,2018,367(2):274-281.
22 Xie W,Zhang Y,Wang B,et al.Tripartite motif containing 24 regulates cell proliferation in colorectal cancer through YAP signaling[J].Cancer Med,2020,9(17):6367-6376.
23 Bergamaschi A,Katzenellenbogen BS.Tamoxifen downregulation of miR-451 increases 14-3-3ζ and promotes breast cancer cell survival and endocrine resistance[J].Oncogene,2012,31(1):39-47.
24 Godbole M,Chandrani P,Gardi N,et al.MiR-129-2 mediates down-regulation of progesterone receptor in response to progesterone in breast cancer cells[J].Cancer Biol Ther,2017,18(10):801-805.
25 Wei S.Hormone receptors in breast cancer:an update on the uncommon subtypes[J].Pathol Res Pract,2023,250:154791.
26 Campbell EJ,Tesson M,Doogan F,et al.The combined endocrine receptor in breast cancer,a novel approach to traditional hormone receptor interpretation and a better discriminator of outcome than ER and PR alone[J].Br J Cancer,2016,115(8):967-973.

[1]	YANG Minye, XIAN Tongcheng, LIU Jingjian, BIE Jun, WANG Jie, LUO Yi. The expression of IL-23 in breast cancer tissues and its correlation with clinicopathological characteristics [J]. Journal of Practical Oncology, 2024, 38(5): 323-329.
[2]	CHEN Yanbo, KONG Dejia, ZHANG Jinfeng, MA Zhigang. Correlation between CYP2D6 gene polymorphism and tamoxifen metabolism in breast cancer patients [J]. PRACTICAL ONCOLOGY JOURNAL, 2019, 33(2): 110-114.
[3]	YU Fei,HU Jing,CHEN Xuesong. Research progress of tamoxifen resistance mechanism in breast cancer [J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(2): 160-164.
[4]	WANG Zetao,LV Fulong,WANG Jinsong. Autophagy facilitates breast cancer cells to resist tamoxifen by p38/c-Jun pathway [J]. PRACTICAL ONCOLOGY JOURNAL, 2015, 29(1): 22-28.

The role and mechanism of TRIM24 in endocrine therapy resistance of breast cancer

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 4

Recommended Articles

Metrics

Comments