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ERβ exerts multiple stimulative effects on human breast carcinoma cells

Oncogene volume 23, pages 5799–5806 (2004)Cite this article

Abstract

Recent studies of ERs in breast cancer have demonstrated the existence of ERβ in addition to ERα. Some clinical data indicated that ERβ had prognostic value for patient's survival, which suggested that ERβ plays a key role in breast cancer development and metastasis. To test this hypothesis, we generated an ERβ high-expression cell line by reintroduced human ERβ cDNA into MDA-MB-435 cells. We demonstrated that ERβ exerted multiple tumor-stimulative effects on human breast carcinoma cells both in vivo and in vitro. In in vitro studies, ERβ was able to increase the proliferation and invasion of MDA-MB-435 cells significantly, while these effects were totally estradiol independent. Also, this stimulation was characterized by downregulation of p21 and upregulation of MMP-9, as well as transcriptional factor Est-1. In in vivo studies, we also demonstrated that ERβ-transfected MDA-MB-435 cells grew much faster and had more pulmonary metastasis than mock or wild-type cells in nude mice. In ERβ-transfected MDA-MB-435 xenografts, ERβ caused significant reduction in p21 protein levels. Similar effects of ERβ on MMP-9 and Ets-1 expression noted in vitro studies were also observed in the in vivo studies. These in vitro and in vivo studies indicated that ERβ exerted multiple stimulative effects on breast cancer development and metastasis.

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References

  • Albini A . (1998). Pathol. Oncol. Res., 4, 230–241.

  • Beato M, Hettlich P and Schutz G . (1995). Cell, 83, 851–857.

  • Bhat RA, Harnish DC, Stevis PE, Lyttle CR and Komm BS . (1988). J. Steroid Biochem. Mol. Biol., 67, 233–240.

  • Delsal G, Loda M and Pagano M . (1996). Crit. Rev. Oncog., 7, 127–142.

  • Dotslaw H, Leygue E, Watson PH and Murphy LC . (1997). J. Clin. Endocrinol. Metab., 82, 2371–2374.

  • Dotslaw H, Leygue E, Watson PH and Murphy LC . (1999). Cancer Res., 59, 529–532.

  • Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjold M and Gustafsson JA . (1997). J. Clin. Endocrinol. Metab., 82, 4258–4265.

  • Folkman J . (1990). Cancer Metastasis Rev., 9, 171–174.

  • Haggitt RC . (1994). Hum. Pathol., 25, 982–993.

  • Higashino F, Yoshida K, Noumi T, Seiki M and Fujinaga K . (1995). Oncogene, 10, 1461–1463.

  • Hu YF, Lau KM, Ho SM and Russo J . (1998). Int. J. Oncol., 12, 1225–1228.

  • Iurlaro M, Loverro G, Vacca A, Cormio G, Ribatti D, Minischetti M, Ria R, Bruno M and Selvaggi L . (1999). Eur. J. Clin. Invest., 29, 793–801.

  • Irwin JC, Kirk D, Gwatkin RB, Navre M, Cannon P and Giudice LC . (1996). J. Clin. Invest., 97, 438–447.

  • Jarvinen TA, Pelto-Huikko M, Holli K and Isola J . (2000). Am. J. Pathol., 156, 29–35.

  • Kuiper GG, Enmark E, Pelto-Hhuikko M, Nilsson S and Gustafsson JA . (1996). Proc. Natl. Acad. Sci. USA, 93, 5925–5930.

  • Lazennec G, Bresson D, Lucas A, Chauveau C and Vignon F . (2001). Endocrinology, 142, 4120–4130.

  • Leygue E, Dotslaw H, Watson PH and Murphy LC . (1998). Cancer Res., 58, 3197–3201.

  • Leygue E, Watson PH and Murphy LC . (1997). J. Clin. Endocrinol. Metab., 82, 2371–2374.

  • Mizumoto H, Satto T, Ashihara K, Nishimura M, Tanaka R and Kudo R . (2002). Int. J. Cancer, 100, 401–406.

  • Moore JT, Mckee DD, Slentz-Kesler K, Moore LB, Jones SA, Horne EL, Su JL, Kliewer SA, Lehmann JM and Willson TM . (1998). Biochem. Biophys. Res. Commun., 247, 75–78.

  • Mosselman S, Polman J and Dijkema R . (1996). FEBS Lett., 392, 49–53.

  • Nakayama T, Ito M, Ohtsuru A, Naito S and Sekne I . (2001). Mod. Pathol., 14, 415–422.

  • Ogawa S, Inoue S, Watanabe T, Hiroi H, Orimo A, Hosoi T, Ouchi Y and Muramatsu M . (1998). Biochem. Biophys. Res. Commun., 243, 122–126.

  • Palmieri C, Cheng GJ, Saji S, Zelada-Hedman M, Warri A, Weihua Z, van Noorden S, Wahlstrom T, Coombes RC, Warner M and Gustafsson JA . (2002). Endocrine-Relat. Cancer., 9, 1–13.

  • Saeki H, Kuwano H, Kawaguchi H, Ohno S and Sugimachi K . (2000). Cancer, 89, 1670–1676.

  • Shao ZM, Nguyen M, Alpaugh ML, O'Connel JT and Barsky SH . (1998). Exp. Cell Res., 241, 394–403.

  • Shao ZM, Shen ZZ, Liu CH, Sartippour MR, Go VL, Heber D and Nguyen M . (2002). Int. J. Cancer, 98, 234–240.

  • Sherr CJ . (1996). Science, 274, 1672–1677.

  • Sillem M, Prifti S, Koumouridis A and Runnebaum B . (1999). Eur. J. Gynaecol. Oncol., 20, 367–370.

  • Tonetti DA, Rubenstein R, Deleon M, Zhao H, Pappas SG, Bentrem DJ, Chen B, Constantinou A and Jordan VC . (2003). J. Steroid Biochem. Mol. Biol., 87, 47–55.

  • Urquidi V, Sloan D, Kawai K, Agarwal D, Woodman AC, Tarin D and Goodison S . (2002). Clin. Cancer Res., 8, 61–74.

  • Van Golen KL, Risin S, Staroselsky A, Berger D, Tainsky MA, Pathak S and Price JE . (1996). Clin. Exp. Metastasis, 14, 95–106.

  • Wen XF, Shen Z, Shen ZZ, Nguyen M and Shao ZM . (2002). Oncol. Rep., 9, 937–944.

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Acknowledgements

This research was supported in part by the Outstanding Young Investigator Award of National Natural Science Foundation of China (30025015) and National Key Project of China (2001BA703BO5) and The Project of Medical Star of Shanghai Health Bureau.

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Author notes

  1. Yi-Feng Hou and Sheng-Tao Yuan: These authors contributed equally to the work

Authors and Affiliations

  1. Department of Surgery, Cancer Hospital/Cancer Institute, Fudan University, Shanghai, 200032, People's Republic of China

    Yi-Feng Hou, He-Cheng Li, Jiong Wu, Jin-Song Lu, Gang Liu, Zhen-Zhou Shen & Zhi-Ming Shao

  2. Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Material Medica, Chinese Academy of Sciences, People's Republic of China

    Sheng-Tao Yuan, Li-Juan Lu & Jian Ding

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  1. Yi-Feng Hou
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Correspondence to Jian Ding or Zhi-Ming Shao.

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Hou, YF., Yuan, ST., Li, HC. et al. ERβ exerts multiple stimulative effects on human breast carcinoma cells. Oncogene 23, 5799–5806 (2004). https://doi.org/10.1038/sj.onc.1207765

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