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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Reduced Expression of RBP7 is Associated with Resistance to Tamoxifen In Luminal A Breast Cancer

Author(s): Xiaolu Yan*, Zhe Gao, Lixia Zhang and Chuan Chen*

Volume 23, Issue 8, 2023

Published on: 11 January, 2023

Page: [929 - 937] Pages: 9

DOI: 10.2174/1871520623666221219090047

Price: $65

Abstract

Background: Tamoxifen is the most commonly used hormonal treatment for ERα-positive breast cancer. Tamoxifen resistance is still a big problem for ERα target therapy. RBP7 is a member of the cellular retinol-binding protein family.

Objective: This study aims to investigate the prognostic role of RBP7 and the relationship between RBP7 expression and sensitivity or resistance to tamoxifen in ERα-positive breast cancer.

Methods: A bioinformatics method was used to investigate RBP7 expression and the prognostic value of RBP7 in different subtypes of breast cancer. The relationship between RBP7 expression and sensitivity or resistance to tamoxifen was studied using clinical data (GSE1379) and cell line data (GSE27473, GSE2645923, GSM3715281, and GSM3715282). Transfection of RBP7 experiments was used to testify to the function of RBP7 in MCF7 cell.

Results: RBP7 is a member of the family of cellular retinol-binding proteins. RBP7 expression was down-regulated at both mRNA and protein levels in breast cancer and was not associated with different TNM (Tumor, Node, Metastasis) stages. High expression of RBP7 was significantly related to good relative percent survival in the luminal A subtype, but in negative breast cancer, the result was opposite. The ROC plot showed that RBP7 had a significant predictive value for the tamoxifen response in the luminal A subtype. The expression of RBP7 from patients with recurrence treated with tamoxifen was significantly reduced. Gene Expression Omnibus showed that RBP7 expression was reduced considerably in tamoxifen-resistant MCF7 cells and T47D cells. The expression of RBP7 was positively correlated with some microRNAs involved in negatively regulating tamoxifen-resistant breast cancer. We also found that the expression of RBP7 decreased significantly in tamoxifen-resistant MCF7 cells, and transfection of RBP7 increased the sensitivity of resistant cells to tamoxifen.

Conclusion: Reduced expression of RBP7 is associated with resistance to tamoxifen in luminal A breast cancer. Our research may help to explore the mechanisms of resistance of breast cancer to tamoxifen.

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[1]
Dai, X.; Cheng, H.; Bai, Z.; Li, J. Breast cancer cell line classification and its relevance with breast tumor subtyping. J. Cancer, 2017, 8(16), 3131-3141.
[http://dx.doi.org/10.7150/jca.18457] [PMID: 29158785]
[2]
Tecalco-Cruz, A.C.; Ramírez-Jarquín, J.O.; Cruz-Ramos, E. Estrogen receptor alpha and its ubiquitination in breast cancer cells. Curr. Drug Targets, 2019, 20(6), 690-704.
[http://dx.doi.org/10.2174/1389450119666181015114041] [PMID: 30324876]
[3]
Rani, A.; Stebbing, J.; Giamas, G.; Murphy, J. Endocrine resistance in hormone receptor positive breast cancer–from mechanism to therapy. Front. Endocrinol., 2019, 10, 245.
[http://dx.doi.org/10.3389/fendo.2019.00245] [PMID: 31178825]
[4]
Chien, T.J. A review of the endocrine resistance in hormone-positive breast cancer. Am. J. Cancer Res., 2021, 11(8), 3813-3831.
[PMID: 34522451]
[5]
Davies, C.; Godwin, J.; Gray, R.; Clarke, M.; Cutter, D.; Darby, S.; McGale, P.; Pan, H.C.; Taylor, C.; Wang, Y.C.; Dowsett, M.; Ingle, J.; Peto, R. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials. Lancet, 2011, 378(9793), 771-784.
[http://dx.doi.org/10.1016/S0140-6736(11)60993-8] [PMID: 21802721]
[6]
Napoli, J.L. Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases. Pharmacol. Ther., 2017, 173, 19-33.
[http://dx.doi.org/10.1016/j.pharmthera.2017.01.004] [PMID: 28132904]
[7]
Piantedosi, R.; Ghyselinck, N.; Blaner, W.S.; Vogel, S. Cellular retinol-binding protein type III is needed for retinoid incorporation into milk. J. Biol. Chem., 2005, 280(25), 24286-24292.
[http://dx.doi.org/10.1074/jbc.M503906200] [PMID: 15870066]
[8]
Ahn, J.; Kim, D.H.; Suh, Y.; Lee, J.W.; Lee, K. Adipose-specific expression of mouse Rbp7 gene and its developmental and metabolic changes. Gene, 2018, 670, 38-45.
[http://dx.doi.org/10.1016/j.gene.2018.05.101] [PMID: 29803924]
[9]
Yu, S.; Cao, W.Q.; Kashireddy, P.; Meyer, K.; Jia, Y.; Hughes, D.E.; Tan, Y.; Feng, J.; Yeldandi, A.V.; Rao, M.S.; Costa, R.H.; Gonzalez, F.J.; Reddy, J.K. Human peroxisome proliferator-activated receptor alpha (PPARalpha) supports the induction of peroxisome proliferation in PPARalpha-deficient mouse liver. J. Biol. Chem., 2001, 276(45), 42485-42491.
[http://dx.doi.org/10.1074/jbc.M106480200] [PMID: 11551940]
[10]
Woll, A.W.; Quelle, F.W.; Sigmund, C.D. PPARγ and retinol binding protein 7 form a regulatory hub promoting antioxidant properties of the endothelium. Physiol. Genomics, 2017, 49(11), 653-658.
[http://dx.doi.org/10.1152/physiolgenomics.00055.2017] [PMID: 28916634]
[11]
Fang, S.; Sigmund, C.D. PPARγ and RhoBTB1 in hypertension. Curr. Opin. Nephrol. Hypertens., 2020, 29(2), 161-170.
[http://dx.doi.org/10.1097/MNH.0000000000000579] [PMID: 31789920]
[12]
Elmasry, M.; Brandl, L.; Engel, J.; Jung, A.; Kirchner, T.; Horst, D. RBP7 is a clinically prognostic biomarker and linked to tumor invasion and EMT in colon cancer. J. Cancer, 2019, 10(20), 4883-4891.
[http://dx.doi.org/10.7150/jca.35180] [PMID: 31598160]
[13]
Qiu, H.; Hu, X.; He, C.; Yu, B.; Li, Y.; Li, J. Identification and validation of an individualized prognostic signature of bladder cancer based on seven immune related genes. Front. Genet., 2020, 11, 12.
[http://dx.doi.org/10.3389/fgene.2020.00012] [PMID: 32117435]
[14]
Jin, K.; Qiu, S.; Jin, D.; Zhou, X.; Zheng, X.; Li, J.; Liao, X.; Yang, L.; Wei, Q. Development of prognostic signature based on immune-related genes in muscle-invasive bladder cancer: bioinformatics analysis of TCGA database. Aging, 2021, 13(2), 1859-1871.
[http://dx.doi.org/10.18632/aging.103787] [PMID: 33465047]
[15]
Li, T.; Fan, J.; Wang, B.; Traugh, N.; Chen, Q.; Liu, J.S.; Li, B.; Liu, X.S. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res., 2017, 77(21), e108-e110.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0307] [PMID: 29092952]
[16]
Li, T.; Fu, J.; Zeng, Z.; Cohen, D.; Li, J.; Chen, Q.; Li, B.; Liu, X.S. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res., 2020, 48(W1), W509-W514.
[http://dx.doi.org/10.1093/nar/gkaa407] [PMID: 32442275]
[17]
Chandrashekar, D.S.; Bashel, B.; Balasubramanya, S.A.H.; Creighton, C.J.; Ponce-Rodriguez, I.; Chakravarthi, B.V.S.K.; Varambally, S. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia, 2017, 19(8), 649-658.
[http://dx.doi.org/10.1016/j.neo.2017.05.002] [PMID: 28732212]
[18]
Liu, C.J.; Hu, F.F.; Xia, M.X.; Han, L.; Zhang, Q.; Guo, A.Y. GSCALite: A web server for gene set cancer analysis. Bioinformatics, 2018, 34(21), 3771-3772.
[http://dx.doi.org/10.1093/bioinformatics/bty411] [PMID: 29790900]
[19]
Lánczky, A.; Győrffy, B. Web-based survival analysis tool tailored for medical research (KMplot): Development and implementation. J. Med. Internet Res., 2021, 23(7)e27633
[http://dx.doi.org/10.2196/27633] [PMID: 34309564]
[20]
Fekete, J.T.; Győrffy, B. ROCplot.org: Validating predictive biomarkers of chemotherapy/hormonal therapy/anti‐HER2 therapy using transcriptomic data of 3,104 breast cancer patients. Int. J. Cancer, 2019, 145(11), 3140-3151.
[http://dx.doi.org/10.1002/ijc.32369] [PMID: 31020993]
[21]
Ma, X.J.; Wang, Z.; Ryan, P.D.; Isakoff, S.J.; Barmettler, A.; Fuller, A.; Muir, B.; Mohapatra, G.; Salunga, R.; Tuggle, J.T.; Tran, Y.; Tran, D.; Tassin, A.; Amon, P.; Wang, W.; Wang, W.; Enright, E.; Stecker, K.; Estepa-Sabal, E.; Smith, B.; Younger, J.; Balis, U.; Michaelson, J.; Bhan, A.; Habin, K.; Baer, T.M.; Brugge, J.; Haber, D.A.; Erlander, M.G.; Sgroi, D.C. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell, 2004, 5(6), 607-616.
[http://dx.doi.org/10.1016/j.ccr.2004.05.015] [PMID: 15193263]
[22]
Gonzalez-Malerva, L.; Park, J.; Zou, L.; Hu, Y.; Moradpour, Z.; Pearlberg, J.; Sawyer, J.; Stevens, H.; Harlow, E.; LaBaer, J. High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc. Natl. Acad. Sci. USA, 2011, 108(5), 2058-2063.
[http://dx.doi.org/10.1073/pnas.1018157108] [PMID: 21233418]
[23]
Zhou, J.; Li, W.; Ming, J.; Yang, W.; Lu, L.; Zhang, Q.; Ruan, S.; Huang, T. High expression of TRAF4 predicts poor prognosis in tamoxifen-treated breast cancer and promotes tamoxifen resistance. Anticancer Drugs, 2020, 31(6), 558-566.
[http://dx.doi.org/10.1097/CAD.0000000000000943] [PMID: 32304412]
[24]
Zhou, J.; Xu, M.; Le, K.; Ming, J.; Guo, H.; Ruan, S.; Huang, T. SRC promotes tamoxifen resistance in breast cancer via up-regulating SIRT1. OncoTargets Ther., 2020, 13, 4635-4647.
[http://dx.doi.org/10.2147/OTT.S245749] [PMID: 32547094]
[25]
Al Saleh, S.; Al Mulla, F.; Luqmani, Y.A. Estrogen receptor silencing induces epithelial to mesenchymal transition in human breast cancer cells. PLoS One, 2011, 6(6)e20610
[http://dx.doi.org/10.1371/journal.pone.0020610] [PMID: 21713035]
[26]
Zhu, Y.; Liu, Y.; Zhang, C.; Chu, J.; Wu, Y.; Li, Y.; Liu, J.; Li, Q.; Li, S.; Shi, Q.; Jin, L.; Zhao, J.; Yin, D.; Efroni, S.; Su, F.; Yao, H.; Song, E.; Liu, Q. Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1. Nat. Commun., 2018, 9(1), 1595.
[http://dx.doi.org/10.1038/s41467-018-03951-0] [PMID: 29686231]
[27]
Nicolini, A.; Ferrari, P.; Duffy, M.J. Prognostic and predictive biomarkers in breast cancer: Past, present and future. Semin. Cancer Biol., 2018, 52(Pt 1), 56-73.
[http://dx.doi.org/10.1016/j.semcancer.2017.08.010] [PMID: 28882552]
[28]
Zhang, X.; Mu, X.; Huang, O.; Xie, Z.; Jiang, M.; Geng, M.; Shen, K. Luminal breast cancer cell lines overexpressing ZNF703 are resistant to tamoxifen through activation of Akt/mTOR signaling. PLoS One, 2013, 8(8)e72053
[http://dx.doi.org/10.1371/journal.pone.0072053] [PMID: 23991038]
[29]
Chu, R.; van Hasselt, A.; Vlantis, A.C.; Ng, E.K.W.; Liu, S.Y.W.; Fan, M.D.; Ng, S.K.; Chan, A.B.W.; Liu, Z.; Li, X.; Chen, G.G. The cross-talk between estrogen receptor and peroxisome proliferator-activated receptor gamma in thyroid cancer. Cancer, 2014, 120(1), 142-153.
[http://dx.doi.org/10.1002/cncr.28383] [PMID: 24114184]
[30]
Loo, S.Y.; Syn, N.L.; Koh, A.P.F.; Teng, J.C.F.; Deivasigamani, A.; Tan, T.Z.; Thike, A.A.; Vali, S.; Kapoor, S.; Wang, X.; Wang, J.W.; Tan, P.H.; Yip, G.W.; Sethi, G.; Huang, R.Y.J.; Hui, K.M.; Wang, L.; Goh, B.C.; Kumar, A.P. Epigenetic derepression converts PPARγ into a druggable target in triple-negative and endocrine-resistant breast cancers. Cell Death Discov., 2021, 7(1), 265.
[http://dx.doi.org/10.1038/s41420-021-00635-5] [PMID: 34580286]
[31]
Baranova, A. PPAR ligands as potential modifiers of breast carcinoma outcomes. PPAR Res., 2008, 2008, 1-10.
[http://dx.doi.org/10.1155/2008/230893] [PMID: 18645617]
[32]
Fulan, H.; Changxing, J.; Baina, W.Y.; Wencui, Z.; Chunqing, L.; Fan, W.; Dandan, L.; Dianjun, S.; Tong, W.; Da, P.; Yashuang, Z. Retinol, vitamins A, C, and E and breast cancer risk: A meta-analysis and meta-regression. Cancer Causes Control, 2011, 22(10), 1383-1396.
[http://dx.doi.org/10.1007/s10552-011-9811-y] [PMID: 21761132]

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