Increased vimentin mRNA expression in MCF-7 breast cancer cell line after repeated endoxifen-treatment

  • Paramita Paramita Faculty of Medicine, Universitas Indonesia, Jakarta
  • Melva Louisa Departement of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Nafrialdi Nafrialdi Departement of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta
DOI: https://doi.org/10.13181/mji.v25i4.1397
Keywords: endoxifen, EMT, vimentin
Abstract viewed: 5017 times
PDF downloaded: 1297 times
HTML downloaded: 48 times
EPUB downloaded: 113 times

Abstract

Background: Epithelial mesenchymal transition (EMT) plays a significant role in the development of cancer cell resistance to drugs. Vimentin, a type III intermediate filament protein, is a marker of EMT. Vimentin's over-expression in cancer correlates well with increased tumor growth, change in cell shape and poor prognosis. Endoxifen is an active metabolite of tamoxifen  and has become a new potent agent in the treatment of breast cancer. This is a study that aimed to investigate the effect of endoxifen exposure with or without estradiol on cell viability, cell morphology and EMT progression through the analysis of vimentin mRNA expression after 4-week treatment.

Methods: Endoxifen, 100 nM or 1,000 nM, with or without beta-estradiol were given repeatedly to MCF-7 cells. Cells treated with dimethyl sulfoxide (DMSO) 0.001% were used as control. After 2- and 4-week exposure, the cells were counted, analyzed for mRNA vimentin expression, and observed for morphological changes.

Results: Compared to control, there were significant decreases in vimentin mRNA expressions in endoxifen and endoxifen+β-estradiol treated cells after 2-weeks, which then significantly increased after 4-week compared with the 2-week exposure. We found no change in morphology of MCF-7 cells.

Conclusion: Repeated exposure of endoxifen might induce EMT progression through increased expression of vimentin in MCF-7 breast cancer cell line.

References

  1. Wu X, Hawse JR, Subramaniam M, Goetz MP, Ingle JN, Spelsberg TC. The tamoxifen metabolite, endoxifen, is a potent antiestrogen that targets estrogen receptor alpha for degradation in breast cancer cells. Cancer Res. 2009;69(5):1722-7. https://doi.org/10.1158/0008-5472.CAN-08-3933

  2. Hawse JR, Subramaniam M, Cicek M, Wu X, Gingery A, Grygo SB, et al. Endoxifen's molecular mechanism of action are concentration dependent and different than that of other anti-estrogens. PLoS One. 2013;8(1):e54613. https://doi.org/10.1371/journal.pone.0054613

  3. Hawse JR, Subramaniam M, Wu X, Negron V, Muzaffer C, Lingle WL, et al. Abstract PD05-11: development, characterization, and effective in vitro treatment of an endoxifen resistant breast cancer cell line. Cancer Res. 2010;70(24):1. https://doi.org/10.1158/0008-5472.sabcs10-pd05-11

  4. Housman G, Byler S, Heerboth S, Lapinska K, Longacre M, Snyder N, et al. Drug resistance in cancer: an overview. Cancers. 2014;6(3):1769-92. https://doi.org/10.3390/cancers6031769

  5. Satelli A, Li S. Vimentin in cancer and its potential molecular target in cancer therapy. Cell Mol Life Sci. 2012;68(18):3033-46. https://doi.org/10.1007/s00018-011-0735-1

  6. Mendez MG, Kojima S, Goldman RD. Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J. 2010;24(6):1838-51. https://doi.org/10.1096/fj.09-151639

  7. Micalizzi DS, Farabaugh SM, Ford HL. Epithelial-mesenchymal transition in cancer: parallels between normal development and tumor progression. J Mammary Gland Biol Neoplasia. 2010;15(2):117-34. https://doi.org/10.1007/s10911-010-9178-9

  8. Savagner P. The epithelial-mesenchymal transition (EMT) phenomenon. Ann Oncol. 2010;21(7):vii89-92. https://doi.org/10.1093/annonc/mdq292

  9. Kalluri R, Weinberg RA. The basic of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420-8. https://doi.org/10.1172/JCI39104

  10. Wang Y, Zhou BP. Epithelial-mesenchymal transition--a hallmark of breast cancer metastasis. Cancer Hallm. 2013;1(1):38-49. https://doi.org/10.1166/ch.2013.1004

  11. Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers, and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796(2):75-90. https://doi.org/10.1016/j.bbcan.2009.03.002

  12. Kusinska RU, Kordek R, Pluciennik E, Bednarek AK, Piekarski JH, Potemski P. Does vimentin help to delineate the so-called 'basal type breast cancer'? J Exp Clin Cancer Res. 2009;28(1):118. https://doi.org/10.1186/1756-9966-28-118

  13. Kidd ME, Shumaker DK, Ridge KM. The role of vimentin intermediate filaments in the progression of lung cancer. Am J Respir Cell Mol Biol. 2014;50(1):1-6. DOI: 10.1165/rcmb.2013-0314TR

  14. Yang J, Bielenberg DR, Rodig SJ, Doiron R, Clifton MC, Kung AL, et al. Lipocalin 2 promotes breast cancer progression. Proc Natl Acad Sci USA. 2009;106(10):3913-8. https://doi.org/10.1073/pnas.0810617106

  15. Folkerd EJ, Lønning PE, Dowsett M. Interpreting plasma estrogen levels in breast cancer: caution needed. J Clin Oncol. 2014;32(14):1396-400. https://doi.org/10.1200/JCO.2013.53.9411

  16. Jamalzadeh L, Ghafoori H, Sariri R, Rabuti H, Nasirzade J, Hasani H, et al. Cytotoxic effects of some common organic solvents on MCF-7, RAW-264.7 and human umbilical vein endothelial cells. Avicenna J Med Biochem. 2016;4(1):e33453. https://doi.org/10.17795/ajmb-33453

  17. Yan XD, Li M, Yuan Y, Mao N, Pan LY. Biological comparison of ovarian cancer resistant cell lines to cisplatin and Taxol by two different administrations. Oncol Rep. 2007;17(5):1163-9. https://doi.org/10.3892/or.17.5.1163

  18. Louie MC, McClellan A, Siewit C, Kawabata L. Estrogen receptor regulates E2F1 expression to mediate tamoxifen resistance. Mol Cancer Res. 2010;8(3):343-52. https://doi.org/10.1158/1541-7786.MCR-09-0395

  19. Carlet J, Jarlier V, Harbarth S, Voss A, Goosens H, Pittet D, et al. Ready for a world without antibiotics? The pensières antibiotic resistance call to action. Antimicrob Resist Infect Control. 2012;1(1):11. https://doi.org/10.1186/2047-2994-1-11

  20. Dong W, Zhang H, Li J, Guan H, He L, Wang Z, et al. Estrogen induces metastatic potential of papillary thyroid cancer cells through estrogen receptor α and β. Int J Endocrinol. 2013;2013(941568):1-6. https://doi.org/10.1155/2013/941568

  21. Jiménez-Salazar JE, Posadas-Rodríguez P, Lazzarini-Lechuga RC, Luna-López A, Zentella-Dehesa A, Gómez-Quiroz LE, et al. Membrane-initiated estradiol signaling of epithelial-mesenchymal transition-associated mechanisms through regulation of tight junctions in human breast cancer cells. Horm Cancer. 2014;5(3):161–73. https://doi.org/10.1007/s12672-014-0180-3

  22. Zhao G, Nie Y, Lv M, He L, Wang T, Hou Y. ERβ-mediated estradiol enhances epithelial mesenchymal transition of lung adenocarcinoma through increasing transcription of midkine. Mol Endocrinol. 2012;26(8):1304-15. https://doi.org/10.1210/me.2012-1028

Published
2017-01-25
How to Cite
1.
Paramita P, Louisa M, Nafrialdi N. Increased vimentin mRNA expression in MCF-7 breast cancer cell line after repeated endoxifen-treatment. Med J Indones [Internet]. 2017Jan.25 [cited 2024Apr.20];25(4):207-13. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/1397
Issue
Vol. 25 No. 4 (2016): December
Section
Basic Medical Research

Copyright (c) 2017 Paramita Paramita, Melva Louisa, Nafrialdi Nafrialdi

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Authors who publish with Medical Journal of Indonesia agree to the following terms:

  1. Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
  2. Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.

Most read articles by the same author(s)