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Cellular and Molecular Biology Letters

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Volume 12, Issue 2


Phenol red in the culture medium strongly affects the susceptibility of human MCF-7 cells to roscovitine

Józefa Węsierska-Gądek
  • Cell Cycle Regulation Group, Division: Institute of Cancer Research, Department of Medicine I, Vienna Medical University, Borschkegasse 8 a, A-1090, Vienna, Austria
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/ Tanja Schreiner
  • Cell Cycle Regulation Group, Division: Institute of Cancer Research, Department of Medicine I, Vienna Medical University, Borschkegasse 8 a, A-1090, Vienna, Austria
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/ Margarita Maurer
  • Cell Cycle Regulation Group, Division: Institute of Cancer Research, Department of Medicine I, Vienna Medical University, Borschkegasse 8 a, A-1090, Vienna, Austria
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/ Astrid Waringer
  • Cell Cycle Regulation Group, Division: Institute of Cancer Research, Department of Medicine I, Vienna Medical University, Borschkegasse 8 a, A-1090, Vienna, Austria
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/ Carmen Ranftler
  • Cell Cycle Regulation Group, Division: Institute of Cancer Research, Department of Medicine I, Vienna Medical University, Borschkegasse 8 a, A-1090, Vienna, Austria
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Published Online: 2007-01-19 | DOI: https://doi.org/10.2478/s11658-007-0002-5


Estrogens play an important role in the growth and terminal differentiation of the mammary gland. Prolonged exposure to estrogens seems to predispose women to breast cancer. It recently became evident that not only the intrinsic hormonal status but also external factors such as the occurrence of pharmaceuticals and chemicals with hormone activity in the environment may put women at greater risk of developing breast cancer. We focused on the interference of endocrine disruptors in breast cancer therapy. We observed that phenol red added to the culture medium strongly promoted the cell proliferation and cell cycle progression of human cells expressing the estrogen receptor, and affected their susceptibility to chemotherapy.

Keywords: Endocrine disrupters; Apoptosis; Cell cycle arrest; Cyclin-dependent inhibitors

  • [1] Hulka, B.S. and Stark, A.T. Breast cancer: cause and prevention. Lancet 346 (1995) 883–887. http://dx.doi.org/10.1016/S0140-6736(95)92713-1CrossrefGoogle Scholar

  • [2] Martin, A.M. and Weber, B.L. Genetic and hormonal risk factors in breast cancer. J. Natl. Cancer Inst. 92 (2000) 1126–1135. http://dx.doi.org/10.1093/jnci/92.14.1126CrossrefGoogle Scholar

  • [3] Green, S., Walter, P., Kumar, V., Krust, A., Bornert, J.M, Argos, P. and Chambon, P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb A. Nature 320 (1986) 134–139. http://dx.doi.org/10.1038/320134a0CrossrefGoogle Scholar

  • [4] Greene, G.L, Gilna, P., Waterfield, M., Baker, A., Hort, Y. and Shine, J. Sequence and expression of human estrogen receptor complementary DNA. Science 231 (1986) 1150–1154. http://dx.doi.org/10.1126/science.3753802CrossrefGoogle Scholar

  • [5] Kuiper, G.G., Enmark, E., Pelto-Huikko, M., Nilsson, S. and Gustafsson, J.A. Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. USA 93 (1996) 5925–5930. http://dx.doi.org/10.1073/pnas.93.12.5925CrossrefGoogle Scholar

  • [6] Evans, R.M. The steroid and thyroid hormone receptor superfamily. Science 240 (1988) 889–895. http://dx.doi.org/10.1126/science.3283939CrossrefGoogle Scholar

  • [7] Beato, M. Gene regulation by steroid hormones. Cell 56 (1989) 335–344. http://dx.doi.org/10.1016/0092-8674(89)90237-7CrossrefGoogle Scholar

  • [8] Ham, J. and Parker, M.G. Regulation of gene expression by nuclear hormone receptors. Curr. Opin. Cell Biol. 1 (1989) 503–511. http://dx.doi.org/10.1016/0955-0674(89)90012-4CrossrefGoogle Scholar

  • [9] Gronemeyer, H. Transcription activation by extrogen and progesteron receptors. Annu. Rev. Gen. 25 (1991) 89–123. http://dx.doi.org/10.1146/annurev.ge.25.120191.000513CrossrefGoogle Scholar

  • [10] Sukovich, D.A., Mukherjee, R. and Benfield, P.A. A novel, cell-type specific mechanism for estrogen receptor-mediated gene activation in the absence of an estrogen-responsive element. Mol. Cell. Biol. 14 (1994) 7134–7143. Google Scholar

  • [11] Liu, J. and Sidell, N. Anti-estrogenic effects of conjugated linoleic acid through modulation of estrogen receptor phosphorylation. Breast Cancer Res. Treat. 94 (2005) 161–169. http://dx.doi.org/10.1007/s10549-005-6942-4CrossrefGoogle Scholar

  • [12] Devarajan, E., Sahin, A.A., Chen, J.S., Krishnamurthy, R.R., Aggarwal, N., Brun, A.M., Saprino, A., Zhang, F., Sharma, D., Yang, X.H. Tora, A.D. and Mehta, K. Down-regulation of caspase-3 in breast cancer: a possible mechanism for chemoresistance. Oncogene 21 (2002) 8843–8851. http://dx.doi.org/10.1038/sj.onc.1206044CrossrefGoogle Scholar

  • [13] Wesierska Gadek, J., Gueorguieva, M. and Horky, M. Dual action of cyclin-dependent kinase inhibitors: induction of cell cycle arrest and apoptosis. A comparison of the effects exerted by roscovitine and cisplatin. Polish J. Pharmacol. 55 (2003) 895–902. Google Scholar

  • [14] Jänicke, R.U., Sprengart, M.L., Wati, M.R. and Porter, A.G. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J. Biol. Chem. 273 (1998) 9357–9360. http://dx.doi.org/10.1074/jbc.273.16.9357CrossrefGoogle Scholar

  • [15] Yonish-Rouach, E., Resnitzky, D., Lotem, J., Sachs, L., Kimchi, A. and Oren, M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature 352 (1991) 345–347. http://dx.doi.org/10.1038/352345a0Google Scholar

  • [16] Kovar, H., Jug, G., Printz, D., Bartl, S., Schmid, G. and Wesierska-Gadek, J. Characterization of distinct consecutive phases in non-genotoxic p53-induced apoptosis of Ewing tumor cells and the rate-limiting role of caspase 8. Oncogene 19 (2000) 4096–4107. http://dx.doi.org/10.1038/sj.onc.1203780CrossrefGoogle Scholar

  • [17] Haupt, S., Berger, M., Goldberg, Z. and Haupt, Y. Apoptosis — the p53 network. J. Cell Sci. 116 (2003) 4077–4085. http://dx.doi.org/10.1242/jcs.00739Google Scholar

  • [18] Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y. and Taya, Y. p53AIP1, a potent mediator of p53-dependent apoptosis, and its regulation bySer-46-phosphorylated p53. Cell 102 (2000) 849–862. http://dx.doi.org/10.1016/S0092-8674(00)00073-8CrossrefGoogle Scholar

  • [19] Matsuda, K., Yoshida, K., Taya, Y., Nakamura, K., Nakamura, Y. and Arakawa, H. p53AIP1 regulates the mitochondrial apoptotic pathway. Cancer Res. 62 (2002) 2883–2889. Google Scholar

  • [20] Wojciechowski, J., Horky, M., Gueorguieva, M. and Wesierska-Gadek, J. Rapid onset of nucleolar disintegration preceding cell cycle arrest in roscovitine-induced apoptosis of human MCF-7 breast cancer cells. Int. J. Cancer 106 (2003) 486–495. http://dx.doi.org/10.1002/ijc.11290CrossrefGoogle Scholar

  • [21] Wesierska Gadek, J., Gueorguieva, M. and Horky, M. Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells. Mol. Cancer Ther. 4 (2005) 113–124. http://dx.doi.org/10.4161/cbt.4.1.1446CrossrefGoogle Scholar

  • [22] Wesierska-Gadek, J., Schreiner, T., Gueorguieva, M. and Ranftler, C. Phenol red reduces ROSC mediated cell cycle arrest and apoptosis in human MCF-7 cells. J. Cell. Biochem. 98 (2006) 1367–1379. http://dx.doi.org/10.1002/jcb.20960CrossrefGoogle Scholar

  • [23] Wesierska-Gadek, J., Schloffer, D., Gueorguieva, M., Uhl, M. and Skladanowski, A. Increased susceptibility of poly(ADP-ribose) polymerase-1 knockout cells to antitumor triazoloacridone C-1305 is associated with permanent G2 cell cycle arrest. Cancer Res. 64 (2004) 4487–4497. http://dx.doi.org/10.1158/0008-5472.CAN-03-3410CrossrefGoogle Scholar

  • [24] Wesierska-Gadek, J., Gueorguieva, M., Ranftler, C. and Zerza-Schnitzhofer, G. A new multiplex assay allowing simultaneous detection of the inhibition of cell proliferation and induction of cell death. J. Cell. Biochem. 96 (2005) 1–7. http://dx.doi.org/10.1002/jcb.20531CrossrefGoogle Scholar

  • [25] Wesierska-Gadek, J. and Schmid, G. Overexpressed poly(ADP-ribose) polymerase delays the release of rat cells from p53-mediated G1 checkpoint. J. Cell. Biochem. 80 (2000) 85–103. http://dx.doi.org/10.1002/1097-4644(20010101)80:1<85::AID-JCB80>3.0.CO;2-1CrossrefGoogle Scholar

  • [26] Vindelov, L.L., Christensen, I.J. and Nissen, N.J. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3 (1983) 323–327. http://dx.doi.org/10.1002/cyto.990030503CrossrefGoogle Scholar

  • [27] Schiff, R. and Fuqua S. 2002. The importance of the estrogen receptor in breast cancer. In: Pasqualini L. (ed.) Breast cancer: prognosis, treatment and prevention. Marcel Dekker Inc. New York, pp. 149–186. Google Scholar

  • [28] Speirs, V. Oestrogen receptor beta in breast cancer: good, bad or still to early to tell? J. Pathol. 19 (2002) 143–147. http://dx.doi.org/10.1002/path.1072CrossrefGoogle Scholar

  • [29] Parl, F.F. 2000. Estrogens, estrogen receptors and breast cancer. IOS Press, Ohmsha, Amsterdam. Google Scholar

  • [30] Hall, J.M., Couse, J.F. and Korrach, K.S. The multifaceted mechanisms of estradiol and estrogen receptor signaling. J. Biol. Chem. 276 (2001) 36869–36872. http://dx.doi.org/10.1074/jbc.R100029200CrossrefGoogle Scholar

  • [31] Hilakivi-Clarke, L. Estrogens, BRCA1, and breast cancer. Cancer Res. 60 (2000) 4993–5001. Google Scholar

  • [32] Marquis, S.T., Rajan, J.V., Wynshaw-Boris, A., Xu, J., Yin, G-Y., Abel, K.J., Weber, B. and Chodosh, L.A. The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues. Nature Genet. 11 (1995) 17–26. http://dx.doi.org/10.1038/ng0995-17CrossrefGoogle Scholar

  • [33] Gudas, J.M., Nguyen, H., Li, T. and Cowan, K.H. Hormone-dependent regulation of BRCA1 in human breast cancer cells. Cancer Res. 55 (1995) 4561–4565. Google Scholar

  • [34] Spillman, M.A. and Bowcock, A.M. BRCA1 and BRCA2 mRNA levels are coordinately elevated in human breast cancer cells in response to estrogen. Oncogene 13 (1996) 1639–1645. Google Scholar

  • [35] Hurd, C., Khattree, N., Dinda, S., Alban, A. and Moudgil, V.K. Regulation of tumor suppressor proteins, p53 and retinoblastoma, by estrogen and antiestrogens in breast cancer cells. Oncogene 15 (1997) 991–995. http://dx.doi.org/10.1038/sj.onc.1201233CrossrefGoogle Scholar

  • [36] Berthois, Y., Katzenellenbogen, J.A. and Katzenellenbogen, B.S. Phenol red in tissue culture media is a weak estrogen: Implications concerning the study of estrogen-responsive cells in culture. Proc. Natl. Acad. Sci. USA 83 (1986) 2496–2500. http://dx.doi.org/10.1073/pnas.83.8.2496CrossrefGoogle Scholar

  • [37] Zwijsen, R.M., Wientjens, E., Klompmaker, R., van der Sman, J., Bernards, E. and Michalides, R.J. CDK-independent activation of estrogen receptor by cyclin D1. Cell 88 (1997) 405–415. http://dx.doi.org/10.1016/S0092-8674(00)81879-6CrossrefGoogle Scholar

  • [38] Neuman, E., Ladha, M.H., Lin, N., Upton, T.M., Miller, S.J., DiRenzo, J., Pestell, R.G., Hinds, P.W., Dowdy, S.F., Brown, M. and Ewen, M.E. Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol. Cell. Biol. 17 (1997) 5338–5347. Google Scholar

  • [39] Martin, L.A., Farmer, I., Johnston, S.R., Ali, S., Marshall, C. and Dowsett, M. Enhanced estrogen receptor (ER)α, ERBB2, and MAPK signal transduction pathways during the adaptation of MCF-7 cells to long term estrogen deprivation. J. Biol. Chem. 278 (2003) 30458–30468. http://dx.doi.org/10.1074/jbc.M305226200CrossrefGoogle Scholar

  • [40] Santen, R.J., Lobenhofer, E.K., Afshari, C.A., Bao, Y. and Song, R.X. Adaptation of estrogen-regulated genes in long-term estradiol deprived MCF-7 breast cancer cells. Breast Cancer Res. Treat. 94 (2005) 213–223. http://dx.doi.org/10.1007/s10549-005-5776-4CrossrefGoogle Scholar

About the article

Published Online: 2007-01-19

Published in Print: 2007-04-01

Citation Information: Cellular and Molecular Biology Letters, Volume 12, Issue 2, Pages 280–293, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-007-0002-5.

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© 2007 University of Wrocław, Poland. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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