nach oben

Breast Cancer Research and Treatment

Erschienen in:

01.01.2012 | Preclinical study

miRNA-34a is associated with docetaxel resistance in human breast cancer cells

verfasst von: L. Kastl, I. Brown, A. C. Schofield

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2012

Einloggen, um Zugang zu erhalten

Abstract

Docetaxel is a chemotherapy drug to treat breast cancer, however as with many chemotherapeutic drugs resistance to docetaxel occurs in 50% of patients, and the underlying molecular mechanisms of drug resistance are not fully understood. Gene regulation through microRNAs (miRNA) has been shown to play an important role in cancer drug resistance. By directly targeting mRNA, miRNAs are able to inhibit genes that are necessary for signalling pathways or drug induced apoptosis rendering cells drug resistant. This study investigated the role of differential miRNA expression in two in vitro breast cancer cell line models (MCF-7, MDA-MB-231) of acquired docetaxel resistance. MiRNA microarray analysis identified 299 and 226 miRNAs altered in MCF-7 and MDA-MB-231 docetaxel-resistant cells, respectively. Docetaxel resistance was associated with increased expression of miR-34a and miR-141 and decreased expression of miR-7, miR-16, miR-30a, miR-125a-5p, miR-126. Computational target prediction revealed eight candidate genes targeted by these miRNAs. Quantitative PCR and western analysis confirmed decreased expression of two genes, BCL-2 and CCND1, in docetaxel-resistant cells, which are both targeted by miR-34a. Modulation of miR-34a expression was correlated with BCL-2 and cyclin D1 protein expression changes and a direct interaction of miR-34a with BCL-2 was shown by luciferase assay. Inhibition of miR-34a enhanced response to docetaxel in MCF-7 docetaxel-resistant cells, whereas overexpression of miR-34a conferred resistance in MCF-7 docetaxel-sensitive cells. This study is the first to show differences in miRNA expression, in particular, increased expression of miR-34a in an acquired model of docetaxel resistance in breast cancer. This serves as a mechanism of acquired docetaxel resistance in these cells, possibly through direct interactions with BCL-2 and CCND1, therefore presenting a potential therapeutic target for the treatment of docetaxel-resistant breast cancer.

Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, Ah-See AK, Eremin O, Walker LG, Sarkar TK, Eggleton SP, Ogston KN (2002) Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 20:1456–1466PubMedCrossRef

Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM (2005) Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol 23:5542–5551PubMedCrossRef

Modok S, Mellor HR, Callaghan R (2006) Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr Opin Pharmacol 6:350–354PubMedCrossRef

Miyoshi Y, Taguchi T, Kim SJ, Tamaki Y, Noguchi S (2005) Prediction of response to docetaxel by immunohistochemical analysis of CYP3A4 expression in human breast cancers. Breast Cancer 12:11–15PubMedCrossRef

Noguchi S (2006) Predictive factors for response to docetaxel in human breast cancers. Cancer Sci 97:813–820PubMedCrossRef

Shalli K, Brown I, Heys SD, Schofield AC (2005) Alterations of beta-tubulin isotypes in breast cancer cells resistant to docetaxel. FASEB J 19:1299–1301PubMed

Kastl L, Brown I, Schofield AC (2010) Altered DNA methylation is associated with docetaxel resistance in human breast cancer cells. Int J Oncol 36:1235–1241PubMed

Zhang XT, Yashiro M, Ren J, Hirakawa K (2006) Histone deacetylase inhibitor, trichostatin A, increases the chemosensitivity of anticancer drugs in gastric cancer cell lines. Oncol Rep 16:563–568PubMed

Miska EA (2005) How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev 15:563–568PubMedCrossRef

10.

Ying SY, Chang DC, Lin S (2008) The microRNA (miRNA): overview of the RNA genes that modulate gene function. Mol Biotechnol 38:257–268PubMedCrossRef

11.

Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J, Fan D (2008) miR-15b and miR-16 modulate multidrug resistance by targeting BCL-2 in human gastric cancer cells. Int J Cancer 123:372–379PubMedCrossRef

12.

Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008) Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett 582:1564–1568PubMedCrossRef

13.

Pan YZ, Morris ME, Yu AM (2009) MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol Pharmacol 75:1374–1379PubMedCrossRef

14.

Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S (2008) MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 283:29897–29903PubMedCrossRef

15.

Liang Z, Wu H, Xia J, Li Y, Zhang Y, Huang K, Wagar N, Yoon Y, Cho HT, Scala S, Shim H (2010) Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem Pharmacol 79:817–824PubMedCrossRef

16.

Mei M, Ren Y, Zhou X, Yuan XB, Han L, Wang GX, Jia Z, Pu PY, Kang CS, Yao Z (2010) Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat 9:77–86PubMed

17.

Brown I, Shalli K, McDonald SL, Moir SE, Hutcheon AW, Heys SD, Schofield AC (2004) Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells. Breast Cancer Res 6:601–607CrossRef

18.

Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ (2009) Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J Biol Chem 284:5731–5741

19.

Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102:13944–13949

20.

Liu Q, Fu H, Sun F, Zhang H, Tie Y, Zhu J, Xing R, Sun Z, Zheng X (2008) miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res 36:5391–5404

21.

Nakamoto M, Jin P, O’Donnell WT, Warren ST (2005) Physiological identification of human transcripts translationally regulated by a specific microRNA. Hum Mol Genet 14:3813–3821

22.

Yamakuchi M, Ferlito M, Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 105:13421–13426

23.

Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC (2007) Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 282:1479–1486

24.

Liu B, Peng XC, Zheng XL, Wang J, Qin YW (2009) MiR-126 restoration down-regulate VEGF and inhibit the growth of lung cancer cell lines in vitro and in vivo. Lung Cancer 66:169–175

25.

Beitzinger M, Peters L, Zhu JY, Kremmer E, Meister G (2007) Identification of human microRNA targets from isolated argonaute protein complexes. RNA Biol 4:76–84

26.

Cole KA, Attiyeh EF, Mosse YP, Laquaglia MJ, Diskin SJ, Brodeur GM, Maris JM (2008) A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res 6:735–742PubMedCrossRef

27.

Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, Zheng X (2009) miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett 275:44–53PubMedCrossRef

28.

Fujita Y, Kojima K, Hamada N, Ohhashi R, Akao Y, Nozawa Y, Deguchi T, Ito M (2008) Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun 377:114–119PubMedCrossRef

29.

Kojima K, Fujita Y, Nozawa Y, Deguchi T, Ito M (2010) MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate 70:1501–1512PubMedCrossRef

30.

Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, Meister G, Hermeking H (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6:1586–1593PubMedCrossRef

31.

Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRef

32.

Kent OA, Mendell JT (2006) A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 25:6188–6196PubMedCrossRef

33.

Han EK, Ng SC, Arber N, Begemann M, Weinstein IB (1999) Roles of cyclin D1 and related genes in growth inhibition, senescence and apoptosis. Apoptosis 4:213–219PubMedCrossRef

34.

Biliran H Jr, Wang Y, Banerjee S, Xu H, Heng H, Thakur A, Bollig A, Sarkar FH, Liao JD (2005) Overexpression of cyclin D1 promotes tumor cell growth and confers resistance to cisplatin-mediated apoptosis in an elastase-myc transgene-expressing pancreatic tumor cell line. Clin Cancer Res 11:6075–6086PubMedCrossRef

35.

Henriksson E, Baldetorp B, Borg A, Kjellen E, Akervall J, Wennerberg J, Wahlberg P (2006) p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck. Acta Oncol 45:300–305PubMedCrossRef

36.

Zhang P, Zhang Z, Zhou X, Qiu W, Chen F, Chen W (2006) Identification of genes associated with cisplatin resistance in human oral squamous cell carcinoma cell line. BMC Cancer 6:224PubMedCrossRef

37.

Lukyanova NY, Rusetskya NV, Tregubova NA, Chekhun VF (2009) Molecular profile and cell cycle in MCF-7 cells resistant to cisplatin and doxorubicin. Exp Oncol 31:87–91PubMed

38.

Fan CW, Chan CC, Chao CC, Fan HA, Sheu DL, Chan EC (2004) Expression patterns of cell cycle and apoptosis-related genes in a multidrug-resistant human colon carcinoma cell line. Scand J Gastroenterol 39:464–469PubMedCrossRef

39.

Resnitzky D, Gossen M, Bujard H, Reed SI (1994) Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. Mol Cell Biol 14:1669–1679PubMed

40.

Resnitzky D, Reed SI (1995) Different roles for cyclins D1 and E in regulation of the G1-to-S transition. Mol Cell Biol 15:3463–3469PubMed

41.

Lukas J, Aagaard L, Strauss M, Bartek J (1995) Oncogenic aberrations of p16INK4/CDKN2 and cyclin D1 cooperate to deregulate G1 control. Cancer Res 55:4818–4823PubMed

42.

Lukas J, Pagano M, Staskova Z, Draetta G, Bartek J (1994) Cyclin D1 protein oscillates and is essential for cell cycle progression in human tumour cell lines. Oncogene 9:707–718PubMed

43.

Kim R, Tanabe K, Emi M, Uchida Y, Toge T (2005) Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cells. Cancer 103:2199–2207PubMedCrossRef

44.

Huang Y, Ray S, Reed JC, Ibrado AM, Tang C, Nawabi A, Bhalla K (1997) Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells. Breast Cancer Res Treat 42:73–81PubMedCrossRef

45.

Hori M, Nogami T, Itabashi M, Yoshimi F, Ono H, Koizumi S (1997) Expression of Bcl-2 in human breast cancer: correlation between hormone receptor status, p53 protein accumulation and DNA strand breaks associated with apoptosis. Pathol Int 47:757–762PubMedCrossRef

46.

Elledge RM, Green S, Howes L, Clark GM, Berardo M, Allred DC, Pugh R, Ciocca D, Ravdin P, O’Sullivan J, Rivkin S, Martino S, Osborne CK (1997) bcl-2, p53, and response to tamoxifen in estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group Study. J Clin Oncol 15:1916–1922PubMed

47.

el-Ahmady O, El-Salahy E, Mahmoud M, Wahab MA, Eissa S, Khalifa A (2002) Multivariate analysis of bcl-2, apoptosis, P53 and HER-2/neu in breast cancer: a short-term follow-up. Anticancer Res 22:2493–2499PubMed

48.

Bilalovic N, Vranic S, Hasanagic S, Basić H, Tatarević A, Beslija S, Selak I (2004) The Bcl-2 protein: a prognostic indicator strongly related to ER and PR in breast cancer. Bosn J Basic Med Sci 4:5–12PubMed

49.

Cardoso F, Paesmans M, Larsimont D, Durbecq V, Bernard-Marty C, Rouas G, Dolci S, Sotiriou C, Piccart MJ, Di Leo A (2004) Potential predictive value of Bcl-2 for response to tamoxifen in the adjuvant setting of node-positive breast cancer. Clin Breast Cancer 5:364–369PubMedCrossRef

50.

Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, Zhai Y, Giordano TJ, Qin ZS, Moore BB, MacDougald OA, Cho KR, Fearon ER (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17:1298–1307PubMedCrossRef

51.

Wang X, Liu P, Zhu H, Xu Y, Ma C, Dai X, Huang L, Liu Y, Zhang L, Qin C (2009) miR-34a, a microRNA up-regulated in a double transgenic mouse model of Alzheimer’s disease, inhibits BCL-2 translation. Brain Res Bull 80:268–273PubMedCrossRef

52.

Cicatiello L, Mutarelli M, Grober OM, Paris O, Ferraro L, Ravo M, Tarallo R, Luo S, Schroth GP, Seifert M, Zinser C, Chiusano ML, Traini A, De Bortoli M, Weisz A (2010) Estrogen receptor alpha controls a gene network in luminal-like breast cancer cells comprising multiple transcription factors and microRNAs. Am J Pathol 176:2113–2130PubMedCrossRef

53.

Kondo N, Toyama T, Sugiura H, Fujii Y, Yamashita H (2008) miR-206 Expression is down-regulated in estrogen receptor alpha-positive human breast cancer. Cancer Res 68:5004–5008PubMedCrossRef

Titel: miRNA-34a is associated with docetaxel resistance in human breast cancer cells
verfasst von: L. Kastl
I. Brown
A. C. Schofield
Publikationsdatum: 01.01.2012
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2012
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-011-1424-3

Springer Medizin

miRNA-34a is associated with docetaxel resistance in human breast cancer cells

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2012

The effect of mTOR inhibition alone or combined with MEK inhibitors on brain metastasis: an in vivo analysis in triple-negative breast cancer models

Prognostic impact of isolated tumor cells in breast cancer axillary nodes: single tumor cell(s) versus tumor cell cluster(s) and microanatomic location

The p160 ER co-regulators predict outcome in ER negative breast cancer

Effect of simvastatin on the pharmacokinetics of anastrozole

Change in physical activity during active treatment in a prospective study of breast cancer survivors

BRCA1 c.4987-3C>G is a pathogenic mutation

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie