Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Author(s): Laila Alsawalha, Mamoun Ahram*, Mohammad S. Abdullah and Ozlem Dalmizrak

DOI: 10.2174/1871520622666220509123505

DownloadDownload PDF Flyer Cite As
Enzalutamide Overcomes Dihydrotestosterone-Induced Chemoresistance in Triple- Negative Breast Cancer Cells via Apoptosis

Page: [3038 - 3048] Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: Triple-negative breast cancer is challenging to treat due to its heterogeneity and lack of therapeutic targets. Hence, systemic chemotherapy is still the mainstay in TNBC treatment. Unfortunately, patients commonly develop chemoresistance. Androgen signalling through its receptor is an essential player in breast cancer, where it has been shown to confer chemoresistance to TNBC cells.

Objective: The objective of the study was to elucidate the mechanistic effects of enzalutamide in the chemoresponse of TNBC cells to doxorubicin through the apoptosis pathway.

Methods: MDA-MB-231 and MDA-MB-453 cells were used as model systems of TNBC. Cell viability and apoptosis were investigated upon treatment of cells with doxorubicin in the presence of dihydrotestosterone (DHT) and/or enzalutamide. Caspase 3/7 activity and TUNEL assays were performed to assess the induction of apoptosis. The expression of apoptosis-regulatory genes was assayed by qPCR for the detection of expression changes.

Results: Enzalutamide decreased the viability of MDA-MB-231 and MDA-MB- 453 cells and reduced DHT-induced chemoresistance of both cell lines. It also increased the chemosensitivity towards doxorubicin in MDA-MB-231 cells. Increasing DNA degradation and caspase 3/7 activity were concomitant with these outcomes. Moreover, enzalutamide downregulated the expression of the anti-apoptosis genes, mcl1 and bcl2, in MDA-MB-231 cells, while increasing the expression of the pro-apoptotic gene bid. On the other hand, DHT upregulated the expression of the anti-apoptosis genes, mcl1 and bcl2, in both cell lines.

Conclusion: DHT increased the expression of the anti-apoptosis genes mcl1 and bcl2 in the TNBC cells, presumably leading to cell survival via the prevention of doxorubicin-induced apoptosis. On the other hand, enzalutamide may sensitize the cells to doxorubicin through downregulation of the bid/bcl2/mcl1 axis that normally activates the executive caspases, caspase 3/7. The activities of the latter enzymes were apparent in DNA degradation at the late stages of apoptosis.

Keywords: Triple-negative breast cancer, androgen receptor, dihydrotestosterone, enzalutamide, chemoresistance, apoptosis.

Graphical Abstract

[1]
Ferlay, J.; Colombet, M.; Soerjomataram, I.; Mathers, C.; Parkin, D.M.; Piñeros, M.; Znaor, A.; Bray, F. Estimating the global cancer inci-dence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer, 2019, 144(8), 1941-1953.
[http://dx.doi.org/10.1002/ijc.31937] [PMID: 30350310]
[2]
Matutino, A.; Joy, A.A.; Brezden-Masley, C.; Chia, S.; Verma, S. Hormone receptor-positive, HER2-negative metastatic breast cancer: Redrawing the lines. Curr. Oncol., 2018, 25(June)(Suppl. 1), S131-S141.
[http://dx.doi.org/10.3747/co.25.4000] [PMID: 29910656]
[3]
Barton, V.N.; D’Amato, N.C.; Gordon, M.A.; Christenson, J.L.; Elias, A.; Richer, J.K. Androgen receptor biology in triple negative breast cancer: A case for classification as AR+ or quadruple negative disease. Horm. Cancer, 2015, 6(5-6), 206-213.
[http://dx.doi.org/10.1007/s12672-015-0232-3] [PMID: 26201402]
[4]
Bauer, K.R.; Brown, M.; Cress, R.D.; Parise, C.A.; Caggiano, V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: A population-based study from the California cancer Registry. Cancer, 2007, 109(9), 1721-1728.
[http://dx.doi.org/10.1002/cncr.22618] [PMID: 17387718]
[5]
Zhu, Y.; Liu, C.; Armstrong, C.; Lou, W.; Sandher, A.; Gao, A.C. Antiandrogens inhibit ABCB1 efflux and ATPase activity and reverse docetaxel resistance in advanced prostate cancer. Clin. Cancer Res., 2015, 21(18), 4133-4142.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0269] [PMID: 25995342]
[6]
D’Amato, N.C.; Gordon, M.A.; Babbs, B.; Spoelstra, N.S.; Carson Butterfield, K.T.; Torkko, K.C.; Phan, V.T.; Barton, V.N.; Rogers, T.J.; Sartorius, C.A.; Elias, A.; Gertz, J.; Jacobsen, B.M.; Richer, J.K. Cooperative dynamics of AR and ER activity in breast cancer. Mol. Cancer Res., 2016, 14(11), 1054-1067.
[http://dx.doi.org/10.1158/1541-7786.MCR-16-0167] [PMID: 27565181]
[7]
Guedj, M.; Marisa, L.; de Reynies, A.; Orsetti, B.; Schiappa, R.; Bibeau, F.; MacGrogan, G.; Lerebours, F.; Finetti, P.; Longy, M.; Bertheau, P.; Bertrand, F.; Bonnet, F.; Martin, A.L.; Feugeas, J.P.; Bièche, I.; Lehmann-Che, J.; Lidereau, R.; Birnbaum, D.; Bertucci, F.; de Thé, H.; Theillet, C. A refined molecular taxonomy of breast cancer. Oncogene, 2012, 31(9), 1196-1206.
[http://dx.doi.org/10.1038/onc.2011.301] [PMID: 21785460]
[8]
Tran, C.; Ouk, S.; Clegg, N. J.; Chen, Y.; Watson, P. A.; Arora, V.; Wongvipat, J.; Smith-Jones, P. M.; Yoo, D.; Kwon, A.; Wasielewska, T.; Welsbie, D.; Chen, C. D.; Higano, C. S.; Beer, T. M.; Hung, D. T.; Scher, H. I.; Jung, M. E.; Sawyers, C. L. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science (80-. ), 2009, 324(5928), 787-790.
[http://dx.doi.org/10.1126/science.1168175]
[9]
Traina, T.A.; Miller, K.; Yardley, D.A.; Eakle, J.; Schwartzberg, L.S.; O’Shaughnessy, J.; Gradishar, W.; Schmid, P.; Winer, E.; Kelly, C.; Nanda, R.; Gucalp, A.; Awada, A.; Garcia-Estevez, L.; Trudeau, M.E.; Steinberg, J.; Uppal, H.; Tudor, I.C.; Peterson, A.; Cortes, J. Enzalu-tamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J. Clin. Oncol., 2018, 36(9), 884-890.
[http://dx.doi.org/10.1200/JCO.2016.71.3495] [PMID: 29373071]
[10]
Lee, Y.M.; Oh, M.H.; Go, J.H.; Han, K.; Choi, S.Y. Molecular subtypes of triple-negative breast cancer: Understanding of subtype catego-ries and clinical implication. Genes Genomics, 2020, 42(12), 1381-1387.
[http://dx.doi.org/10.1007/s13258-020-01014-7] [PMID: 33145728]
[11]
Housman, G.; Byler, S.; Heerboth, S.; Lapinska, K.; Longacre, M.; Snyder, N.; Sarkar, S. Drug resistance in cancer: An overview. Cancers (Basel), 2014, 6(3), 1769-1792.
[http://dx.doi.org/10.3390/cancers6031769] [PMID: 25198391]
[12]
Hassan, M.; Watari, H.; AbuAlmaaty, A.; Ohba, Y.; Sakuragi, N. Apoptosis and molecular targeting therapy in cancer. Bio. Med Res. Int., 2014, 2014, 150845.
[http://dx.doi.org/10.1155/2014/150845] [PMID: 25013758]
[13]
McNamara, K.M.; Yoda, T.; Miki, Y.; Nakamura, Y.; Suzuki, T.; Nemoto, N.; Miyashita, M.; Nishimura, R.; Arima, N.; Tamaki, K.; Ishida, T.; Ohuchi, N.; Sasano, H. Androgen receptor and enzymes in lymph node metastasis and cancer reoccurrence in triple-negative breast cancer. Int. J. Biol. Markers, 2015, 30(2), e184-e189.
[http://dx.doi.org/10.5301/jbm.5000132] [PMID: 25588857]
[14]
Santer, F.R.; Erb, H.H.H.; Oh, S.J.; Handle, F.; Feiersinger, G.E.; Luef, B.; Bu, H.; Schäfer, G.; Ploner, C.; Egger, M.; Rane, J.K.; Maitland, N.J.; Klocker, H.; Eder, I.E.; Culig, Z. Mechanistic rationale for MCL1 inhibition during androgen deprivation therapy. Oncotarget, 2015, 6(8), 6105-6122.
[http://dx.doi.org/10.18632/oncotarget.3368] [PMID: 25749045]
[15]
Galluzzi, L.; Kepp, O.; Kroemer, G. Caspase-3 and prostaglandins signal for tumor regrowth in cancer therapy. Oncogene, 2012, 31(23), 2805-2808.
[http://dx.doi.org/10.1038/onc.2011.459] [PMID: 21963852]
[16]
Al-Momany, B.; Hammad, H.; Ahram, M. Dihydrotestosterone induces chemo-resistance of triple-negative breast MDA-MB-231 cancer cells towards doxorubicin independent of ABCG2 and miR-328-3p. Curr. Mol. Pharmacol., 2021, 14(5), 860-870.
[http://dx.doi.org/10.2174/1874467214666210531170355] [PMID: 34061013]
[17]
Al-Othman, N.; Hammad, H.; Ahram, M. Dihydrotestosterone regulates expression of CD44 via miR-328-3p in triple-negative breast can-cer cells. Gene, 2018, 675(June), 128-135.
[http://dx.doi.org/10.1016/j.gene.2018.06.094] [PMID: 29964098]
[18]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(Δ Δ C(T)). Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[19]
Rueden, C.T.; Schindelin, J.; Hiner, M.C.; DeZonia, B.E.; Walter, A.E.; Arena, E.T.; Eliceiri, K.W. ImageJ2: ImageJ for the next generation of scientific image data. BMC Bioinformatics, 2017, 18(1), 529.
[http://dx.doi.org/10.1186/s12859-017-1934-z] [PMID: 29187165]
[20]
Schneider, C.A.; Rasband, W.S.; Eliceiri, K.W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods, 2012, 9(7), 671-675.
[http://dx.doi.org/10.1038/nmeth.2089] [PMID: 22930834]
[21]
Lyons, T.G.; Traina, T.A. Androgen receptor-targeted therapy for breast cancer. Curr. Breast Cancer Rep., 2017, 9(4), 242-250.
[http://dx.doi.org/10.1007/s12609-017-0261-8]
[22]
Simões-Wüst, A.P.; Schürpf, T.; Hall, J.; Stahel, R.A.; Zangemeister-Wittke, U. Bcl-2/bcl-xL bispecific antisense treatment sensitizes breast carcinoma cells to doxorubicin, paclitaxel and cyclophosphamide. Breast Cancer Res. Treat., 2002, 76(2), 157-166.
[http://dx.doi.org/10.1023/A:1020543004400] [PMID: 12452453]
[23]
Virág, L.; Robaszkiewicz, A.; Rodriguez-Vargas, J.M.; Oliver, F.J. Poly(ADP-ribose) signaling in cell death. Mol. Aspects Med., 2013, 34(6), 1153-1167.
[http://dx.doi.org/10.1016/j.mam.2013.01.007] [PMID: 23416893]
[24]
Lamkanfi, M.; Kanneganti, T.D. Caspase-7: A protease involved in apoptosis and inflammation. Int. J. Biochem. Cell Biol., 2010, 42(1), 21-24.
[http://dx.doi.org/10.1016/j.biocel.2009.09.013] [PMID: 19782763]
[25]
Rokhlin, O.W.; Taghiyev, A.F.; Guseva, N.V.; Glover, R.A.; Chumakov, P.M.; Kravchenko, J.E.; Cohen, M.B. Androgen regulates apopto-sis induced by TNFR family ligands via multiple signaling pathways in LNCaP. Oncogene, 2005, 24(45), 6773-6784.
[http://dx.doi.org/10.1038/sj.onc.1208833] [PMID: 16007156]
[26]
Shankar, E.; Franco, D.; Iqbal, O.; Moreton, S.; Kanwal, R.; Gupta, S. Dual targeting of EZH2 and androgen receptor as a novel therapy for castration-resistant prostate cancer. Toxicol. Appl. Pharmacol., 2020, 404(August), 115200.
[http://dx.doi.org/10.1016/j.taap.2020.115200] [PMID: 32805266]
[27]
Pan, S.T.; Li, Z.L.; He, Z.X.; Qiu, J.X.; Zhou, S.F. Molecular mechanisms for tumour resistance to chemotherapy. Clin. Exp. Pharmacol. Physiol., 2016, 43(8), 723-737.
[http://dx.doi.org/10.1111/1440-1681.12581] [PMID: 27097837]
[28]
Shimizu, K.; Gi, M.; Suzuki, S.; North, B.J.; Watahiki, A.; Fukumoto, S.; Asara, J.M.; Tokunaga, F.; Wei, W.; Inuzuka, H. Interplay be-tween protein acetylation and ubiquitination controls MCL1 protein stability. Cell Rep., 2021, 37(6), 109988.
[http://dx.doi.org/10.1016/j.celrep.2021.109988] [PMID: 34758305]
[29]
Wuillème-Toumi, S.; Robillard, N.; Gomez, P.; Moreau, P.; Le Gouill, S.; Avet-Loiseau, H.; Harousseau, J.L.; Amiot, M.; Bataille, R. Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival. Leukemia, 2005, 19(7), 1248-1252.
[http://dx.doi.org/10.1038/sj.leu.2403784] [PMID: 15902294]
[30]
Bai, X.; Ni, J.; Beretov, J.; Graham, P.; Li, Y. Triple-negative breast cancer therapeutic resistance: Where is the Achilles’ heel? Cancer Lett., 2021, 497, 100-111.
[http://dx.doi.org/10.1016/j.canlet.2020.10.016] [PMID: 33069769]
[31]
Oyesanya, R. A.; Dasgupta, S.; Dent, P.; Grant, S. Targeting Mcl-1 for the therapy of cancer., 2012, 20(10), 1397-1411.
[32]
Hutchinson, K.E.; Nixon, M.J.; Estrada, M.V.; Sánchez, V.; Sanders, M.E.; Lee, T.; Gómez, H.; Lluch, A.; Pérez-fidalgo, A.; Wolf, M.M.; Andrejeva, G.; Jeffrey, C.; Fesik, S.W.; Arteaga, C.L.; Lee, K.; Giltnane, J.M.; Balko, J.M.; Schwarz, L.J.; Guerrero-Zotano, A.L.; Hutchinson, K.E.; Nixon, M.J.; Estrada, M.V.; Sánchez, V.; Sanders, M.E.; Lee, T.; Gómez, H.; Lluch, A.; Pérez-Fidalgo, J.A.; Wolf, M.M.; Andrejeva, G.; Rathmell, J.C.; Fesik, S.W.; Arteaga, C.L. MYC and MCL1 cooperatively promote chemotherapy- resistant breast cancer stem cells via regulation of mitochondrial oxidative phosphorylation. Cell Metab., 2018, 26(4), 633-647.
[http://dx.doi.org/10.1016/j.cmet.2017.09.009.MYC]
[33]
Mehta, J.; Asthana, S.; Mandal, C.C.; Saxena, S. A molecular analysis provides novel insights into androgen receptor signalling in breast cancer. PLoS One, 2015, 10(3), e0120622.
[http://dx.doi.org/10.1371/journal.pone.0120622] [PMID: 25781993]
[34]
Bing, L.; Wu, J.; Zhang, J.; Chen, Y.; Hong, Z.; Zu, H. DHT inhibits the Aβ25-35-induced apoptosis by regulation of seladin-1, survivin, XIAP, bax, and bcl-xl expression through a rapid PI3-K/Akt signaling in C6 glial cell lines. Neurochem. Res., 2015, 40(1), 41-48.
[http://dx.doi.org/10.1007/s11064-014-1463-3] [PMID: 25347962]
[35]
Inao, T.; Iida, Y.; Moritani, T.; Okimoto, T.; Tanino, R.; Kotani, H.; Harada, M. Bcl-2 inhibition sensitizes triple-negative human breast cancer cells to doxorubicin. Oncotarget, 2018, 9(39), 25545-25556.
[http://dx.doi.org/10.18632/oncotarget.25370] [PMID: 29876007]
[36]
De Amicis, F.; Thirugnansampanthan, J.; Cui, Y.; Beyer, A.; Parra, I.; Weigel, N.L.; Herynk, M.H.; Lewis, M.T.; Chamness, G.C.; Hilsenbeck, S.G.; Fuqua, S.A.W. NIH Public Access., 2010, 121(1), 1-11.
[http://dx.doi.org/10.1007/s10549-009-0436-8.Androgen]
[37]
Nedeljković, M.; Damjanović, A. Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the chal-lenge. Cells, 2019, 8(9), E957.
[http://dx.doi.org/10.3390/cells8090957] [PMID: 31443516]
[38]
Zhu, A.; Li, Y.; Song, W.; Xu, Y.; Yang, F.; Zhang, W.; Yin, Y.; Guan, X. Antiproliferative effect of androgen receptor inhibition in mes-enchymal stem-like triple-negative breast cancer. Cell. Physiol. Biochem., 2016, 38(3), 1003-1014.
[http://dx.doi.org/10.1159/000443052] [PMID: 26938985]
[39]
Jiang, H.S.; Kuang, X.Y.; Sun, W.L.; Xu, Y.; Zheng, Y.Z.; Liu, Y.R.; Lang, G.T.; Qiao, F.; Hu, X.; Shao, Z.M. Androgen receptor expres-sion predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status. Oncotarget, 2016, 7(27), 41285-41293.
[http://dx.doi.org/10.18632/oncotarget.9778] [PMID: 27285752]
[40]
Pietri, E.; Conteduca, V.; Andreis, D.; Massa, I.; Melegari, E.; Sarti, S.; Cecconetto, L.; Schirone, A.; Bravaccini, S.; Serra, P.; Fedeli, A.; Maltoni, R.; Amadori, D.; De Giorgi, U.; Rocca, A. Androgen receptor signaling pathways as a target for breast cancer treatment. Endocr. Relat. Cancer, 2016, 23(10), R485-R498.
[http://dx.doi.org/10.1530/ERC-16-0190] [PMID: 27528625]
[41]
Shen, Y.; Yang, F.; Zhang, W.; Song, W.; Liu, Y.; Guan, X. The androgen receptor promotes cellular proliferation by suppression of G-protein coupled estrogen receptor signaling in triple-negative breast cancer. Cell. Physiol. Biochem., 2017, 43(5), 2047-2061.
[http://dx.doi.org/10.1159/000484187] [PMID: 29059676]
[42]
Chavez, K.J.; Garimella, S.V.; Lipkowitz, S. Triple negative breast cancer cell lines: One tool in the search for better treatment of triple negative breast cancer. Breast Dis., 2010, 32(1-2), 35-48.
[http://dx.doi.org/10.3233/BD-2010-0307] [PMID: 21778573]
[43]
Chottanapund, S.; Van Duursen, M.B.M.; Navasumrit, P.; Hunsonti, P.; Timtavorn, S.; Ruchirawat, M.; Van den Berg, M. Effect of andro-gens on different breast cancer cells co-cultured with or without breast adipose fibroblasts. J. Steroid Biochem. Mol. Biol., 2013, 138, 54-62.
[http://dx.doi.org/10.1016/j.jsbmb.2013.03.007] [PMID: 23562642]
[44]
Ahram, M.; Bawadi, R.; Abdullah, M.S.; Alsafadi, D.B.; Abaza, H.; Abdallah, S.; Mustafa, E. Involvement of β-catenin in androgen-induced mesenchymal transition of breast MDA-MB-453 cancer cells. Endocr. Res., 2021, 46(3), 114-128.
[http://dx.doi.org/10.1080/07435800.2021.1895829] [PMID: 33703980]
[45]
Ahram, M.; Mustafa, E.; Abu Hammad, S.; Alhudhud, M.; Bawadi, R.; Tahtamouni, L.; Khatib, F.; Zihlif, M. The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells. Endocr. Res., 2018, 43(3), 203-214.
[http://dx.doi.org/10.1080/07435800.2018.1455105] [PMID: 29578828]
[46]
McNamara, K.M.; Yoda, T.; Miki, Y.; Chanplakorn, N.; Wongwaisayawan, S.; Incharoen, P.; Kongdan, Y.; Wang, L.; Takagi, K.; Mayu, T.; Nakamura, Y.; Suzuki, T.; Nemoto, N.; Miyashita, M.; Tamaki, K.; Ishida, T.; Ohuchi, N.; Sasano, H. Androgenic pathway in triple negative invasive ductal tumors: Its correlation with tumor cell proliferation. Cancer Sci., 2013, 104(5), 639-646.
[http://dx.doi.org/10.1111/cas.12121] [PMID: 23373898]
[47]
Park, I.H.; Yang, H.N.; Jeon, S.Y.; Hwang, J.A.; Kim, M.K.; Kong, S.Y.; Shim, S.H.; Lee, K.S. Anti-tumor activity of BET inhibitors in androgen-receptor-expressing triple-negative breast cancer. Sci. Rep., 2019, 9(1), 13305.
[http://dx.doi.org/10.1038/s41598-019-49366-9] [PMID: 31527644]
[48]
Nadiminty, N. Tummala, R.; Liu, C.; Yang, J.; Lou, W.; Evans, C.P.; Gao, A.C. NF-κB2/p52 induces resistance to enzalutamide in prostate cancer: Role of androgen receptor and its variants. Mol. Cancer Ther., 2013, 12(8), 1629-1637.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0027] [PMID: 23699654]
[49]
Gerratana, L.; Basile, D.; Buono, G.; De Placido, S.; Giuliano, M.; Minichillo, S.; Coinu, A.; Martorana, F.; De Santo, I.; Del Mastro, L.; De Laurentiis, M.; Puglisi, F.; Arpino, G. Androgen receptor in triple negative breast cancer: A potential target for the targetless subtype. Cancer Treat. Rev., 2018, 68(April), 102-110.
[http://dx.doi.org/10.1016/j.ctrv.2018.06.005] [PMID: 29940524]
[50]
Leone, G.; Buttigliero, C.; Pisano, C.; Di Stefano, R.F.; Tabbò, F.; Turco, F.; Vignani, F.; Scagliotti, G.V.; Di Maio, M.; Tucci, M. Bipolar androgen therapy in prostate cancer: Current evidences and future perspectives. Crit. Rev. Oncol. Hematol., 2020, 152, 102994.
[http://dx.doi.org/10.1016/j.critrevonc.2020.102994] [PMID: 32480269]
[51]
Anestis, A.; Zoi, I.; Papavassiliou, A.G.; Karamouzis, M.V. Androgen receptor in breast cancer-clinical and preclinical research insights. Molecules, 2020, 25(2), 1-11.
[http://dx.doi.org/10.3390/molecules25020358] [PMID: 31952272]
[52]
Yuan, F.; Hankey, W.; Wu, D.; Wang, H.; Somarelli, J.; Armstrong, A.J.; Huang, J.; Chen, Z.; Wang, Q. Molecular determinants for enzalu-tamide-induced transcription in prostate cancer. Nucleic Acids Res., 2019, 47(19), 10104-10114.
[http://dx.doi.org/10.1093/nar/gkz790] [PMID: 31501863]
[53]
Xia, X.; Huang, C.; Liao, Y.; Liu, Y.; He, J.; Guo, Z.; Jiang, L.; Wang, X.; Liu, J.; Huang, H. Inhibition of USP14 enhances the sensitivity of breast cancer to enzalutamide. J. Exp. Clin. Cancer Res., 2019, 38(1), 220.
[http://dx.doi.org/10.1186/s13046-019-1227-7] [PMID: 31126320]
[54]
Thike, A.A.; Yong-Zheng, Chong L.; Cheok, P.Y.; Li, H.H.; Wai-Cheong Yip, G.; Huat Bay, B.; Tse, G.M.K.; Iqbal, J.; Tan, P.H. Loss of androgen receptor expression predicts early recurrence in triple-negative and basal-like breast cancer. Mod. Pathol., 2014, 27(3), 352-360.
[http://dx.doi.org/10.1038/modpathol.2013.145] [PMID: 23929266]
[55]
Al-Othman, N.; Ahram, M.; Alqaraleh, M. Role of androgen and microRNA in triple-negative breast cancer. Breast Dis., 2020, 39(1), 15-27.
[http://dx.doi.org/10.3233/BD-190416] [PMID: 31839601]
[56]
McGhan, L.J.; McCullough, A.E.; Protheroe, C.A.; Dueck, A.C.; Lee, J.J.; Nunez-Nateras, R.; Castle, E.P.; Gray, R.J.; Wasif, N.; Goetz, M.P.; Hawse, J.R.; Henry, T.J.; Barrett, M.T.; Cunliffe, H.E.; Pockaj, B.A. Androgen receptor-positive triple negative breast cancer: A unique breast cancer subtype. Ann. Surg. Oncol., 2014, 21(2), 361-367.
[http://dx.doi.org/10.1245/s10434-013-3260-7] [PMID: 24046116]
[57]
Ahram, M.; Mustafa, E.; Zaza, R.; Abu Hammad, S.; Alhudhud, M.; Bawadi, R.; Zihlif, M. Differential expression and androgen regulation of microRNAs and metalloprotease 13 in breast cancer cells. Cell Biol. Int., 2017, 41(12), 1345-1355.
[http://dx.doi.org/10.1002/cbin.10841] [PMID: 28816390]
[58]
Al-Othman, N.A.; Hammad, H.; Ahram, M. Type of serum as a cell culture supplement influences regulation of MicroRNA expression in breast MDA-MB-231 cancer cells. Al-Magallat al-Tibbiyyat al-Urdunniyyat, 2017, 51(4), 159-165.