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01.04.2019 | Preclinical study

4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion

verfasst von: Gen Wang, Sisi Qin, Jacqueline Zayas, James N. Ingle, Mohan Liu, Richard M. Weinshilboum, Kunwei Shen, Liewei Wang

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2019

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Abstract

Purpose

In early stage, ERα-positive breast cancer, concurrent use of endocrine therapy and chemotherapy has not been shown to be superior to sequential use. We hypothesized that genetic biomarkers can aid in selecting patients who would benefit from chemo-endocrine therapy. Our previous studies revealed that ZNF423 is a transcription factor for BRCA1 and an intronic single nucleotide polymorphism (SNP) in ZNF423, rs9940645, determines tamoxifen response. Here, we identified mitosis-related genes that are regulated by ZNF423 which led us to investigate taxane response in a rs9940645 SNP- and tamoxifen-dependent fashion.

Methods

The Cancer Genome Atlas (TCGA) breast cancer dataset was used to identify genes correlated with ZNF423. Quantitative reverse transcription PCR, chromatin immunoprecipitation, and luciferase reporter assays were used to validate the gene regulation. We used CRISPR/Cas9 to engineer paired ZR-75-1 cells which differ only in ZNF423 rs9940645 SNP genotype to test SNP-dependent phenotypes including cell cycle and cell viability. We validated our findings in an additional two breast cancer cell lines, Hs578T-ERα and HCC1500.

Results

Mitosis-related genes VRK1 and PBK, which encode histone H3 kinases, were experimentally validated to be regulated by ZNF423. ZNF423 knockdown decreased VRK1 and PBK expression and activity. Additionally, ZNF423 knockdown enhanced docetaxel-induced G2/M arrest and cytotoxicity through VRK1 or PBK regulation. Lastly, cells carrying the rs9940645 variant genotype had increased G2/M arrest and decreased cell viability when treated with docetaxel in combination with estradiol and 4-OH-TAM.

Conclusions

We identified ZNF423 regulated genes involved in the G2/M phase of the cell cycle. 4-OH-TAM sensitized ERα-positive breast cancer cells to docetaxel in a ZNF423 SNP-dependent manner. Our findings suggest that patients with rs9940645 variant genotype may benefit from concurrent tamoxifen and docetaxel. This would impact a substantial proportion of patients because this SNP has a minor allele frequency of 0.47.

Nur mit Berechtigung zugänglich

Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA: a cancer journal for clinicians 68 (1):7–30. https://doi.org/10.3322/caac.21442

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210 doiCrossRefPubMed

Albain KS, Barlow WE, Ravdin PM, Farrar WB, Burton GV, Ketchel SJ, Cobau CD, Levine EG, Ingle JN, Pritchard KI, Lichter AS, Schneider DJ, Abeloff MD, Henderson IC, Muss HB, Green SJ, Lew D, Livingston RB, Martino S, Osborne CK (2009) Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet 374(9707):2055–2063. https://doi.org/10.1016/s0140-6736(09)61523-3 CrossRefPubMedPubMedCentral

Bedognetti D, Sertoli MR, Pronzato P, Del Mastro L, Venturini M, Taveggia P, Zanardi E, Siffredi G, Pastorino S, Queirolo P, Gardin G, Wang E, Monzeglio C, Boccardo F, Bruzzi P (2011) Concurrent vs sequential adjuvant chemotherapy and hormone therapy in breast cancer: a multicenter randomized phase III trial. Journal of the National Cancer Institute 103(20):1529–1539. https://doi.org/10.1093/jnci/djr351 CrossRefPubMedPubMedCentral

Sui M, Huang Y, Park BH, Davidson NE, Fan W (2007) Estrogen receptor alpha mediates breast cancer cell resistance to paclitaxel through inhibition of apoptotic cell death. Cancer Res 67(11):5337–5344. https://doi.org/10.1158/0008-5472.can-06-4582 CrossRefPubMed

Ingle JN, Liu M, Wickerham DL, Schaid DJ, Wang L, Mushiroda T, Kubo M, Costantino JP, Vogel VG, Paik S, Goetz MP, Ames MM, Jenkins GD, Batzler A, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM (2013) Selective estrogen receptor modulators and pharmacogenomic variation in ZNF423 regulation of BRCA1 expression: individualized breast cancer prevention. Cancer Discov 3(7):812–825. https://doi.org/10.1158/2159-8290.CD-13-0038 CrossRefPubMedPubMedCentral

Qin S, Ingle JN, Liu M, Yu J, Wickerham DL, Kubo M, Weinshilboum RM, Wang L (2017) Calmodulin-like protein 3 is an estrogen receptor alpha coregulator for gene expression and drug response in a SNP, estrogen, and SERM-dependent fashion. Breast Cancer Res 19(1):95. https://doi.org/10.1186/s13058-017-0890-x CrossRefPubMedPubMedCentral

Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, Billis K, Cummins C, Gall A, Girón CG, Gil L, Gordon L, Haggerty L, Haskell E, Hourlier T, Izuogu OG, Janacek SH, Juettemann T, To JK, Laird MR, Lavidas I, Liu Z, Loveland JE, Maurel T, McLaren W, Moore B, Mudge J, Murphy DN, Newman V, Nuhn M, Ogeh D, Ong CK, Parker A, Patricio M, Riat HS, Schuilenburg H, Sheppard D, Sparrow H, Taylor K, Thormann A, Vullo A, Walts B, Zadissa A, Frankish A, Hunt SE, Kostadima M, Langridge N, Martin FJ, Muffato M, Perry E, Ruffier M, Staines DM, Trevanion SJ, Aken BL, Cunningham F, Yates A, Flicek P (2018) Ensembl 2018. Nucl Acids Res 46(D1):D754–D761. https://doi.org/10.1093/nar/gkx1098 CrossRefPubMed

Liu D, Ho MF, Schaid DJ, Scherer SE, Kalari K, Liu M, Biernacka J, Yee V, Evans J, Carlson E, Goetz MP, Kubo M, Wickerham DL, Wang L, Ingle JN, Weinshilboum RM (2017) Breast cancer chemoprevention pharmacogenomics: deep sequencing and functional genomics of the ZNF423 and CTSO genes. NPJ Breast Cancer 3:30. https://doi.org/10.1038/s41523-017-0036-4 CrossRefPubMedPubMedCentral

10.

Niu N, Qin Y, Fridley BL, Hou J, Kalari KR, Zhu M, Wu TY, Jenkins GD, Batzler A, Wang L (2010) Radiation pharmacogenomics: a genome-wide association approach to identify radiation response biomarkers using human lymphoblastoid cell lines. Genome Res 20(11):1482–1492. https://doi.org/10.1101/gr.107672.110 CrossRefPubMedPubMedCentral

11.

Valbuena A, Sanz-García M, López-Sánchez I, Vega FM, Lazo PA (2011) Roles of VRK1 as a new player in the control of biological processes required for cell division. Cell Signal 23(8):1267–1272. https://doi.org/10.1016/j.cellsig.2011.04.002 CrossRefPubMed

12.

del Puerto-Nevado L, Marin-Arango JP, Fernandez-Aceñero MJ, Arroyo-Manzano D, Martinez-Useros J, Borrero-Palacios A, Rodriguez-Remirez M, Cebrian A, Gomez del Pulgar T, Cruz-Ramos M, Carames C, Lopez-Botet B, Garcia-Foncillas J (2016) Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study. BMC Cancer 16:519. https://doi.org/10.1186/s12885-016-2574-9 CrossRefPubMedPubMedCentral

13.

Huang W, Cui X, Chen Y, Shao M, Shao X, Shen Y, Liu Q, Wu M, Liu J, Ni W, Lu C, Wan C (2016) High VRK1 expression contributes to cell proliferation and survival in hepatocellular carcinoma. Pathol Res Pract 212(3):171–178. https://doi.org/10.1016/j.prp.2015.11.015 CrossRefPubMed

14.

Lee N, Kwon JH, Kim YB, Kim SH, Park SJ, Xu W, Jung HY, Kim KT, Wang HJ, Choi KY (2015) Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition. Oncotarget 6(30):30130–30148. https://doi.org/10.18632/oncotarget.4967 CrossRefPubMedPubMedCentral

15.

Salzano M, Vazquez-Cedeira M, Sanz-Garcia M, Valbuena A, Blanco S, Fernandez IF, Lazo PA (2014) Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response. Oncotarget 5(7):1770–1778. https://doi.org/10.18632/oncotarget.1678 CrossRefPubMedPubMedCentral

16.

Fournier MV, Martin KJ, Kenny PA, Xhaja K, Bosch I, Yaswen P, Bissell MJ (2006) Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Res 66(14):7095–7102. https://doi.org/10.1158/0008-5472.can-06-0515 CrossRefPubMedPubMedCentral

17.

Martin KJ, Patrick DR, Bissell MJ, Fournier MV (2008) Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets. PLoS One 3(8):e2994. https://doi.org/10.1371/journal.pone.0002994 CrossRefPubMedPubMedCentral

18.

Zykova TA, Zhu F, Wang L, Li H, Bai R, Lim DY, Yao K, Bode AM, Dong Z (2017) The T-LAK cell-originated protein kinase signal pathway promotes colorectal cancer metastasis. EBioMedicine 18:73–82. https://doi.org/10.1016/j.ebiom.2017.04.003 CrossRefPubMedPubMedCentral

19.

Ohashi T, Komatsu S, Ichikawa D, Miyamae M, Okajima W, Imamura T, Kiuchi J, Kosuga T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Tsuda H, Otsuji E (2017) Overexpression of PBK/TOPK relates to tumour malignant potential and poor outcome of gastric carcinoma. Br J Cancer 116(2):218–226. https://doi.org/10.1038/bjc.2016.394 CrossRefPubMed

20.

Ohashi T, Komatsu S, Ichikawa D, Miyamae M, Okajima W, Imamura T, Kiuchi J, Nishibeppu K, Kosuga T, Konishi H, Shiozaki A, Fujiwara H, Okamoto K, Tsuda H, Otsuji E (2016) Overexpression of PBK/TOPK contributes to tumor development and poor outcome of esophageal squamous cell carcinoma. Anticancer Res 36(12):6457–6466. https://doi.org/10.21873/anticanres.11244 CrossRefPubMed

21.

Pirovano G, Ashton TM, Herbert KJ, Bryant RJ, Verrill CL, Cerundolo L, Buffa FM, Prevo R, Harrap I, Ryan AJ, Macaulay V, McKenna WG, Higgins GS (2017) TOPK modulates tumour-specific radiosensitivity and correlates with recurrence after prostate radiotherapy. Br J Cancer 117(4):503–512. https://doi.org/10.1038/bjc.2017.197 CrossRefPubMedPubMedCentral

22.

Kang TH, Park DY, Choi YH, Kim KJ, Yoon HS, Kim KT (2007) Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells. Mol Cell Biol 27(24):8533–8546. https://doi.org/10.1128/MCB.00018-07 CrossRefPubMedPubMedCentral

23.

Park JH, Lin ML, Nishidate T, Nakamura Y, Katagiri T (2006) PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative cancer/testis antigen with an oncogenic activity in breast cancer. Cancer Res 66(18):9186–9195. https://doi.org/10.1158/0008-5472.CAN-06-1601 CrossRefPubMed

24.

Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26(14):2373–2378. https://doi.org/10.1200/JCO.2007.14.4287 CrossRef

25.

Gyorffy B, Hatzis C, Sanft T, Hofstatter E, Aktas B, Pusztai L (2015) Multigene prognostic tests in breast cancer: past, present, future. Breast Cancer Res 17:11. https://doi.org/10.1186/s13058-015-0514-2 CrossRefPubMedPubMedCentral

26.

Ades F, Zardavas D, Bozovic-Spasojevic I, Pugliano L, Fumagalli D, de Azambuja E, Viale G, Sotiriou C, Piccart M (2014) Luminal B breast cancer: molecular characterization, clinical management, and future perspectives. J Clin Oncol 32(25):2794–2803. https://doi.org/10.1200/JCO.2013.54.1870 CrossRefPubMed

27.

Casoni F, Croci L, Bosone C, D’Ambrosio R, Badaloni A, Gaudesi D, Barili V, Sarna JR, Tessarollo L, Cremona O, Hawkes R, Warming S, Consalez GG (2017) Zfp423/ZNF423 regulates cell cycle progression, the mode of cell division and the DNA-damage response in Purkinje neuron progenitors. Development 144(20):3686–3697. https://doi.org/10.1242/dev.155077 CrossRefPubMedPubMedCentral

28.

Scharer CD, Laycock N, Osunkoya AO, Logani S, McDonald JF, Benigno BB, Moreno CS (2008) Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells. J Transl Med 6:79. https://doi.org/10.1186/1479-5876-6-79 CrossRefPubMedPubMedCentral

29.

Payton M, Bush TL, Chung G, Ziegler B, Eden P, McElroy P, Ross S, Cee VJ, Deak HL, Hodous BL, Nguyen HN, Olivieri PR, Romero K, Schenkel LB, Bak A, Stanton M, Dussault I, Patel VF, Geuns-Meyer S, Radinsky R, Kendall RL (2010) Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines. Cancer Res 70(23):9846–9854. https://doi.org/10.1158/0008-5472.CAN-10-3001 CrossRefPubMed

30.

Ingle JN (1984) Integration of hormonal agents and chemotherapy for the treatment of women with advanced breast cancer. Mayo Clin Proc 59(4):232–238CrossRefPubMed

31.

Ingle JN, Everson LK, Wieand HS, Martin JK, Votava HJ, Wold LE, Krook JE, Cullinan SA, Paulsen JK, Twito DI et al (1988) Randomized trial of observation versus adjuvant therapy with cyclophosphamide, fluorouracil, prednisone with or without tamoxifen following mastectomy in postmenopausal women with node-positive breast cancer. J Clin Oncol 6(9):1388–1396. https://doi.org/10.1200/jco.1988.6.9.1388 CrossRefPubMed

32.

Ingle JN, Everson LK, Wieand HS, Cullinan SA, Wold LE, Hagen JB, Martin JK, Krook JE, Fitzgibbons RG, Foley JF et al (1989) Randomized trial to evaluate the addition of tamoxifen to cyclophosphamide, 5-fluorouracil, prednisone adjuvant therapy in premenopausal women with node-positive breast cancer. Cancer 63(7):1257–1264CrossRefPubMed

Titel: 4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion
verfasst von: Gen Wang
Sisi Qin
Jacqueline Zayas
James N. Ingle
Mohan Liu
Richard M. Weinshilboum
Kunwei Shen
Liewei Wang
Publikationsdatum: 01.04.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05194-z

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4-Hydroxytamoxifen enhances sensitivity of estrogen receptor α-positive breast cancer to docetaxel in an estrogen and ZNF423 SNP-dependent fashion

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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