gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Loss of tumorigenicity of ER-beta-expressing breast cancer MCF-7 cells

Meeting Abstract

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  • corresponding author presenting/speaker Diana Behrens - Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch, Deutschland
  • Iduna Fichtner - Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch
  • Reiner Zeisig - Max-Delbrück-Centrum für Molekulare Medizin, Berlin-Buch

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO065

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Veröffentlicht: 20. März 2006

© 2006 Behrens et al.
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Introduction: Proliferation of breast cancer cells is mediated by estrogen receptors (ER). Function and mechanism of action of ER-alpha are well known, however, the role of the second ER form - ER-beta - discovered in 1996, for growth and treatment remains to be clarified. At the present, opposing scientific conclusions complicate the functional definition of ER-beta as good or bad prognostic marker. Here we investigated in in vitro and in vivo studies the meaning of ER-beta expression for the viability and the response to (anti)estrogens of the human mammary carcinoma cell line MCF-7.

Methods: For this purpose the ER-alpha-positive breast cancer cell line MCF-7 was stably transfected with the full-length cDNA of ER-beta cloned into a GFP-containing expression vector (pEGFP-N1). Proliferation rate and sensitivity to 17b-estradiol, tamoxifen and ICI 182,780 were monitored by MTT assay. Additionally, cell cycle progression was analysed flow cytometrically and the determination of cell cycle mediating proteins, cyclin A and D1, CDK2, p21Waf1/Cip1, p27Kip1 was carried out by Western Blot. In a second part of the project wild type, empty-vector- as well as ER-beta-transfected MCF-7 cells were transplanted into nude mice to determine the tumorigenicity of these cells.

Results: Transfection of ER-beta cDNA resulted in a 30 % growth inhibition of MCF-7 cells (p = 0.043). Additionally, the in vitro response to estradiol was reversed: MCF-7/ER-beta cells did not raise proliferation rate, they were inhibited to 46 % by estradiol (p = 0.016). However, there was no difference in response to the antiestrogens tamoxifen and ICI 182,780. Importantly, MCF-7/ER-beta cells did not grow as a tumour in immune deficient mice. We found an ER-beta-induced decrease of cyclin A and CDK2 expression resulting in a slower transition through S-phase. Modulation of p21Waf1/Cip1, p27Kip1, cyclin D1 and Ki-67 protein level could not be observed.

Conclusion: ER-beta transfection modified the malignant character of the breast cancer cell line MCF-7 and caused an in vitro and in vivo growth inhibition of these cells by decreasing the expression of cell cycle associated proteins. These findings may evidence that ER-beta acts as tumour suppressor and could serve as a good prognostic marker for ER-beta-positive breast cancer patients. Further investigations are required to prove the idea of exploit ER-beta expression for therapeutic or even preventive purpose.