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Difference between genomic actions of estrogen versus raloxifene in human ovarian cancer cell lines

Oncogene volume 27, pages 2737–2745 (2008)Cite this article

Abstract

Although there is growing evidence that estrogens promote tumor progression in epithelial ovarian cancer, the molecular mechanisms accounting for this are still unclear. Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The molecular mechanisms of the effects of SERMs such as raloxifene on the tumor progression of epithelial ovarian cancer are also still unclear. Here, we show that various genomic actions of estrogen differ from those of raloxifene in human ovarian cancer cell lines expressing estrogen receptor α (ERα). 17β-Estradiol (E2) induced the gene expression of c-Myc and IGF-1 and increased the binding of ERα to the AP1 site of the promoters of c-Myc and IGF-1. ERα silencing abolished the E2-stimulated c-Myc expression. E2 induced the recruitment of co-activators such as SRC-1, SRC-3 and CBP to the promoters of c-Myc and IGF-1, and SRC-1 silencing abolished both the E2-stimulated c-Myc expression and cell-cycle progression. In contrast, although raloxifene increased the binding of ERα to the AP1 site of the promoters of c-Myc and IGF-1, raloxifene had no effect on the gene expression of c-Myc or IGF-1. Raloxifene induced the recruitment of co-repressors such as HDAC2, N-CoR and SMRT to the promoter of IGF-1. Thus, the difference between the genomic actions exerted by estrogen and raloxifene in human ovarian cancer cell lines expressing ERα appear to be dependent on the recruitment of co-regulators.

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Acknowledgements

We are grateful to Ayako Okamura and Tomoko Iwaki for technical and secretarial assistance.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Osaka University Medical School, Yamadaoka, Suita, Osaka, Japan,

    J Hayakawa, H Seino-Noda, M Sakata & K Tasaka

  2. Department of Hematology and Oncology, Osaka University Medical School, Yamadaoka, Suita, Osaka, Japan,

    S Ezoe, I Matsumura & Y Kanakura

  3. Osaka Medical College, Daigakumachi, Takatsuki, Osaka, Japan

    H Sasaki, Y Terai, M Kanemura, A Tanabe-Kimura, H Kamegai & M Ohmichi

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  1. H Sasaki
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  2. J Hayakawa
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Correspondence to M Ohmichi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Sasaki, H., Hayakawa, J., Terai, Y. et al. Difference between genomic actions of estrogen versus raloxifene in human ovarian cancer cell lines. Oncogene 27, 2737–2745 (2008). https://doi.org/10.1038/sj.onc.1210926

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