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Open Access 01-12-2014 | Research article

Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers

Authors: Hang Zhang, Xiyong Liu, Charles D Warden, Yasheng Huang, Sofia Loera, Lijun Xue, Suzhan Zhang, Peiguo Chu, Shu Zheng, Yun Yen

Published in: BMC Cancer | Issue 1/2014

Abstract

Background

Ribonucleotide reductase (RR) is an essential enzyme involved in DNA synthesis. We hypothesized that RR subunit M2 (RRM2) might be a novel prognostic and predictive biomarker for estrogen receptor (ER)-negative breast cancers.

Methods

Individual and pooled survival analyses were conducted on six independent large-scale breast cancer microarray data sets; and findings were validated on a human breast tissue set (ZJU set).

Results

Gene set enrichment analysis revealed that RRM2-high breast cancers were significantly enriched for expression of gene sets that increased in proliferation, invasiveness, undifferentiation, embryonic stem/progenitor-like phenotypes, and poor patient survival (p < 0.01). Independent and pooled analyses verified that increased RRM2 mRNA levels were associated with poor patient outcome in a dose-dependent manner. The prognostic power of RRM2 mRNA was comparable to multiple gene signatures, and it was superior to TNM stage. In ER-negative breast cancers, RRM2 showed more prognostic power than that in ER-positive breast cancers. Further analysis indicated that RRM2 was a more accurate prognostic biomarker for ER-negative breast cancers than the pathoclinical indicators and uPA. A new RR inhibitor, COH29, could significantly enhance the chemosensitivity to doxorubicin in ER-negative MDA-MB-231 cells, but not in ER-positive MCF-7 cells.

Conclusion

RRM2 appears to be a promising prognostic biomarker and therapeutic target for ER-negative breast cancer patients.

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Siegel R, Naishadham D, Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 2013, 63 (1): 11-30. 10.3322/caac.21166.CrossRefPubMed

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale AL: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001, 98 (19): 10869-10874. 10.1073/pnas.191367098.CrossRefPubMedPubMedCentral

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lønning PE, Børresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature. 2000, 406 (6797): 747-752. 10.1038/35021093.CrossRefPubMed

Sorlie T, Wang Y, Xiao C, Johnsen H, Naume B, Samaha RR, Borresen-Dale AL: Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms. BMC Genomics. 2006, 7: 127-10.1186/1471-2164-7-127.CrossRefPubMedPubMedCentral

Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005, 353 (16): 1673-1684. 10.1056/NEJMoa052122.CrossRefPubMed

Andre F, Pusztai L: Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy. Nat Clin Pract. 2006, 3 (11): 621-632. 10.1038/ncponc0636.CrossRef

Nanda R: “Targeting” triple-negative breast cancer: the lessons learned from BRCA1-associated breast cancers. Semin Oncol. 2011, 38 (2): 254-262. 10.1053/j.seminoncol.2011.01.007.CrossRefPubMed

van ’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH: Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002, 415 (6871): 530-536. 10.1038/415530a.CrossRefPubMed

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, Hiller W, Fisher ER, Wickerham DL, Bryant J, Wolmark N: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004, 351 (27): 2817-2826. 10.1056/NEJMoa041588.CrossRefPubMed

10.

Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmstrom P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringnér M, Borg A, Parsons R: Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci U S A. 2007, 104 (18): 7564-7569. 10.1073/pnas.0702507104.CrossRefPubMedPubMedCentral

11.

Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sorlie T, Dai H, He YD, van’t Veer LJ, Bartelink H, van de Rijn M, Brown PO, van de Vijver MJ: Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A. 2005, 102 (10): 3738-3743. 10.1073/pnas.0409462102.CrossRefPubMedPubMedCentral

12.

Ivshina AV, George J, Senko O, Mow B, Putti TC, Smeds J, Lindahl T, Pawitan Y, Hall P, Nordgren H, Wong JE, Liu ET, Bergh J, Kuznetsov VA, Miller LD: Genetic reclassification of histologic grade delineates new clinical subtypes of breast cancer. Cancer Res. 2006, 66 (21): 10292-10301. 10.1158/0008-5472.CAN-05-4414.CrossRefPubMed

13.

Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C: An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol. 2007, 8 (8): R157-10.1186/gb-2007-8-8-r157.CrossRefPubMedPubMedCentral

14.

Staaf J, Ringner M, Vallon-Christersson J, Jonsson G, Bendahl PO, Holm K, Arason A, Gunnarsson H, Hegardt C, Agnarsson BA, Luts L, Grabau D, Fernö M, Malmström PO, Johannsson OT, Loman N, Barkardottir RB, Borg A: Identification of subtypes in human epidermal growth factor receptor 2–positive breast cancer reveals a gene signature prognostic of outcome. J Clin Oncol. 2010, 28 (11): 1813-1820. 10.1200/JCO.2009.22.8775.CrossRefPubMed

15.

Nordlund P, Reichard P: Ribonucleotide reductases. Annu Rev Biochem. 2006, 75: 681-706. 10.1146/annurev.biochem.75.103004.142443.CrossRefPubMed

16.

Jordan A, Reichard P: Ribonucleotide reductases. Annu Rev Biochem. 1998, 67: 71-98. 10.1146/annurev.biochem.67.1.71.CrossRefPubMed

17.

Heidel JD, Liu JY, Yen Y, Zhou B, Heale BS, Rossi JJ, Bartlett DW, Davis ME: Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res. 2007, 13 (7): 2207-2215. 10.1158/1078-0432.CCR-06-2218.CrossRefPubMed

18.

Zhou BS, Tsai P, Ker R, Tsai J, Ho R, Yu J, Shih J, Yen Y: Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential. Clin Exp Metastasis. 1998, 16 (1): 43-49.CrossRefPubMed

19.

Morikawa T, Maeda D, Kume H, Homma Y, Fukayama M: Ribonucleotide reductase M2 subunit is a novel diagnostic marker and a potential therapeutic target in bladder cancer. Histopathology. 2010, 57 (6): 885-892. 10.1111/j.1365-2559.2010.03725.x.CrossRefPubMed

20.

Morikawa T, Hino R, Uozaki H, Maeda D, Ushiku T, Shinozaki A, Sakatani T, Fukayama M: Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects of RRM2 inhibition in vitro. Hum Pathol. 2010, 41 (12): 1742-1748. 10.1016/j.humpath.2010.06.001.CrossRefPubMed

21.

Hsu NY, Wu JY, Liu X, Yen Y, Chen CY, Chou MC, Lin CH, Lee H, Cheng YW: Expression status of ribonucleotide reductase small subunits hRRM2/p53R2 as prognostic biomarkers in stage I and II non-small cell lung cancer. Anticancer Res. 2011, 31 (10): 3475-3481.PubMed

22.

Liu X, Lai L, Wang X, Xue L, Leora S, Wu J, Hu S, Zhang K, Kuo ML, Zhou L, Zhang H, Wang Y, Wang Y, Zhou B, Nelson RA, Zheng S, Zhang S, Chu P, Yen Y: Ribonucleotide reductase small subunit M2B prognoses better survival in colorectal cancer. Cancer Res. 2011, 71 (9): 3202-3213. 10.1158/0008-5472.CAN-11-0054.CrossRefPubMedPubMedCentral

23.

Liu X, Zhang H, Lai L, Wang X, Loera S, Xue L, He H, Zhang K, Hu S, Huang Y, Nelson RA, Zhou B, Zhou L, Chu P, Zhang S, Zheng S, Yen Y: Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers. Clin Sci (Lond). 2013, 124 (9): 567-578. 10.1042/CS20120240.CrossRef

24.

Duxbury MS, Whang EE: RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness. Biochem Biophys Res Commun. 2007, 354 (1): 190-196. 10.1016/j.bbrc.2006.12.177.CrossRefPubMed

25.

Zhang K, Hu S, Wu J, Chen L, Lu J, Wang X, Liu X, Zhou B, Yen Y: Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis. Mol Cancer. 2009, 8: 11-10.1186/1476-4598-8-11.CrossRefPubMedPubMedCentral

26.

Reid G, Wallant NC, Patel R, Antonic A, Saxon-Aliifaalogo F, Cao H, Webster G, Watson JD: Potent subunit-specific effects on cell growth and drug sensitivity from optimised siRNA-mediated silencing of ribonucleotide reductase. J RNAi Gene Silencing. 2009, 5 (1): 321-330.PubMedPubMedCentral

27.

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

28.

Habel LA, Sakoda LC, Achacoso N, Ma XJ, Erlander MG, Sgroi DC, Fehrenbacher L, Greenberg D, Quesenberry CP: HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease. Breast Cancer Res. 2013, 15 (2): R24-10.1186/bcr3402.CrossRefPubMedPubMedCentral

29.

Ma XJ, Salunga R, Dahiya S, Wang W, Carney E, Durbecq V, Harris A, Goss P, Sotiriou C, Erlander M, Sgroi D: A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res. 2008, 14 (9): 2601-2608. 10.1158/1078-0432.CCR-07-5026.CrossRefPubMed

30.

Li Z, Peng L, Han S, Huang Z, Shi F, Cai Z, Li X, Zhang P, Zhu H, Jin W: [Screening molecular markers in early breast cancer of the same pathological types but with different prognoses using Agilent gene chip]. Nan Fang Yi Ke Da Xue Xue Bao. 2013, 33 (10): 1483-1488.PubMed

31.

Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, Nordgren H, Farmer P, Praz V, Haibe-Kains B, Desmedt C, Larsimont D, Cardoso F, Peterse H, Nuyten D, Buyse M, Van de Vijver MJ, Bergh J, Piccart M, Delorenzi M: Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst. 2006, 98 (4): 262-272. 10.1093/jnci/djj052.CrossRefPubMed

32.

Huang E, Cheng SH, Dressman H, Pittman J, Tsou MH, Horng CF, Bild A, Iversen ES, Liao M, Chen CM, West M, Nevins JR, Huang AT: Gene expression predictors of breast cancer outcomes. Lancet. 2003, 361 (9369): 1590-1596. 10.1016/S0140-6736(03)13308-9.CrossRefPubMed

33.

van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R: A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002, 347 (25): 1999-2009. 10.1056/NEJMoa021967.CrossRefPubMed

34.

Chin SF, Wang Y, Thorne NP, Teschendorff AE, Pinder SE, Vias M, Naderi A, Roberts I, Barbosa-Morais NL, Garcia MJ, Iyer NG, Kranjac T, Robertson JF, Aparicio S, Tavaré S, Ellis I, Brenton JD, Caldas C: Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers. Oncogene. 2007, 26 (13): 1959-1970. 10.1038/sj.onc.1209985.CrossRefPubMed

35.

Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, Talantov D, Timmermans M, Meijer-van Gelder ME, Yu J, Jatkoe T, Berns EM, Atkins D, Foekens JA: Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005, 365 (9460): 671-679. 10.1016/S0140-6736(05)17947-1.CrossRefPubMed

36.

Smeds J, Miller LD, Bjohle J, Hall P, Klaar S, Liu ET, Pawitan Y, Ploner A, Bergh J: Gene profile and response to treatment. Ann Oncol. 2005, 16 Suppl 2: ii195-ii202.PubMed

37.

Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, Viale G, Delorenzi M, Zhang Y, d’Assignies MS, Bergh J, Lidereau R, Ellis P, Harris AL, Klijn JG, Foekens JA, Cardoso F, Piccart MJ, Buyse M, Sotiriou C, TRANSBIG Consortium: Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007, 13 (11): 3207-3214. 10.1158/1078-0432.CCR-06-2765.CrossRefPubMed

38.

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP: Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005, 102 (43): 15545-15550. 10.1073/pnas.0506580102.CrossRefPubMedPubMedCentral

39.

Millar EK, Graham PH, McNeil CM, Browne L, O’Toole SA, Boulghourjian A, Kearsley JH, Papadatos G, Delaney G, Fox C, Nasser E, Capp A, Sutherland RL: Prediction of outcome of early ER + breast cancer is improved using a biomarker panel, which includes Ki-67 and p53. Br J Cancer. 2011, 105 (2): 272-280. 10.1038/bjc.2011.228.CrossRefPubMedPubMedCentral

40.

Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, Senn HJ, Panel M: Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011, 22 (8): 1736-1747. 10.1093/annonc/mdr304.CrossRefPubMedPubMedCentral

41.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003, 100 (7): 3983-3988. 10.1073/pnas.0530291100.CrossRefPubMedPubMedCentral

42.

Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM: Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. Proc Natl Acad Sci U S A. 2004, 101 (25): 9309-9314. 10.1073/pnas.0401994101.CrossRefPubMedPubMedCentral

43.

Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G, Palacios J: Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res. 2008, 68 (4): 989-997. 10.1158/0008-5472.CAN-07-2017.CrossRefPubMed

44.

Zhang Y, Crump M, Berge SA: Purging of contaminating breast cancer cells from hematopoietic progenitor cell preparations using activation enhanced cell death. Breast Cancer Res Treat. 2002, 72 (3): 265-278. 10.1023/A:1014965726663.CrossRefPubMed

45.

Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA: An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008, 40 (5): 499-507. 10.1038/ng.127.CrossRefPubMedPubMedCentral

46.

Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, Chi JT, van de Rijn M, Botstein D, Brown PO: Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol. 2004, 2 (2): E7-10.1371/journal.pbio.0020007.CrossRefPubMedPubMedCentral

47.

Naderi A, Teschendorff AE, Barbosa-Morais NL, Pinder SE, Green AR, Powe DG, Robertson JF, Aparicio S, Ellis IO, Brenton JD, Caldas C: A gene-expression signature to predict survival in breast cancer across independent data sets. Oncogene. 2007, 26 (10): 1507-1516. 10.1038/sj.onc.1209920.CrossRefPubMed

48.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295 (21): 2492-2502. 10.1001/jama.295.21.2492.CrossRefPubMed

49.

Urban P, Vuaroqueaux V, Labuhn M, Delorenzi M, Wirapati P, Wight E, Senn HJ, Benz C, Eppenberger U, Eppenberger-Castori S: Increased expression of urokinase-type plasminogen activator mRNA determines adverse prognosis in ErbB2-positive primary breast cancer. J Clin Oncol. 2006, 24 (26): 4245-4253. 10.1200/JCO.2005.05.1912.CrossRefPubMed

50.

Huang Y, Liu X, Wang YH, Yeh SD, Chen CL, Nelson RA, Chu P, Wilson T, Yen Y: The prognostic value of ribonucleotide reductase small subunit M2 in predicting recurrence for prostate cancers. Urol Oncol. 2014, 32 (1): 51-e59-19CrossRefPubMed

51.

Zhou B, Su L, Hu S, Hu W, Yip ML, Wu J, Gaur S, Smith DL, Yuan YC, Synold TW, Horne D, Yen Y: A small-molecule blocking ribonucleotide reductase holoenzyme formation inhibits cancer cell growth and overcomes drug resistance. Cancer Res. 2013, 73 (21): 6484-6493. 10.1158/0008-5472.CAN-13-1094.CrossRefPubMed

52.

Begley CG, Ellis LM: Drug development: raise standards for preclinical cancer research. Nature. 2012, 483 (7391): 531-533. 10.1038/483531a.CrossRefPubMed

53.

Prinz F, Schlange T, Asadullah K: Believe it or not: how much can we rely on published data on potential drug targets?. Nat Rev Drug Discov. 2011, 10 (9): 712-10.1038/nrd3439-c1.CrossRefPubMed

54.

Duxbury MS, Ito H, Zinner MJ, Ashley SW, Whang EE: RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine. Oncogene. 2004, 23 (8): 1539-1548. 10.1038/sj.onc.1207272.CrossRefPubMed

55.

Anderson TJ, Alexander FE, Lamb J, Smith A, Forrest AP: Pathology characteristics that optimize outcome prediction of a breast screening trial. Br J Cancer. 2000, 83 (4): 487-492. 10.1054/bjoc.2000.1286.CrossRefPubMedPubMedCentral

56.

Aimiuwu J, Wang H, Chen P, Xie Z, Wang J, Liu S, Klisovic R, Mims A, Blum W, Marcucci G, Chan KK: RNA-dependent inhibition of ribonucleotide reductase is a major pathway for 5-azacytidine activity in acute myeloid leukemia. Blood. 2012, 119 (22): 5229-5238. 10.1182/blood-2011-11-382226.CrossRefPubMedPubMedCentral

57.

Zhang YW, Jones TL, Martin SE, Caplen NJ, Pommier Y: Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response. J Biol Chem. 2009, 284 (27): 18085-18095. 10.1074/jbc.M109.003020.CrossRefPubMedPubMedCentral

58.

Niida H, Katsuno Y, Sengoku M, Shimada M, Yukawa M, Ikura M, Ikura T, Kohno K, Shima H, Suzuki H, Tashiro S, Nakanishi M: Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase. Genes Dev. 2010, 24 (4): 333-338. 10.1101/gad.1863810.CrossRefPubMedPubMedCentral

59.

Zhou B, Mi S, Mo X, Shih J, Tsai J, Hu E, Hsu M, Kay K, Yen Y: Time and sequence dependence of hydroxyurea in combination with gemcitabine in human KB cells. Anticancer Res. 2002, 22 (3): 1369-1377.PubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/664/prepub

Title: Prognostic and therapeutic significance of ribonucleotide reductase small subunit M2 in estrogen-negative breast cancers
Authors: Hang Zhang
Xiyong Liu
Charles D Warden
Yasheng Huang
Sofia Loera
Lijun Xue
Suzhan Zhang
Peiguo Chu
Shu Zheng
Yun Yen
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-14-664

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