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Estrogen-induced proliferation of normal endometrial glandular cells is initiated by transcriptional activation of cyclin D1 via binding of c-Jun to an AP-1 sequence

Oncogene volume 23, pages 8603–8610 (2004)Cite this article

Abstract

To explore the mechanism of estrogen-induced growth of normal endometrium, the transactivation system of the cyclin D1 gene was analysed using cultured normal endometrial glandular cells. Estradiol (E2) treatment of cultured normal endometrial glandular cells induced upregulation of c-Jun, and then cyclin D1 proteins, followed by serial expressions of cyclins E, A and B1 proteins. Increase in the mRNA expression of cyclin D1 preceded the protein expression of cyclin D1 under E2 treatment. A luciferase assay using deletion constructs of the cyclin D1 promoter indicated that E2-induced increase in transcriptional activity was observed in reporters containing AP-1-binding site sequence, and that in the absence of E2, cotransfection of c-Jun also showed increase of transcriptional activity in the same reporters with AP-1 sequence. A gel shift assay using nuclear extract from E2-treated endometrial glandular cells and AP-1 sequences of the cyclin D1 promoter indicated specific binding between c-Jun protein and the promoter. Transfection of c-jun antisense oligonucleotides to the glandular cells resulted in the suppression of the E2-induced upregulation of cyclin D1 mRNA and protein. These findings suggest that E2-induced proliferation of normal endometrial glandular cells is initiated by transcriptional activation of cyclin D1 via binding of c-Jun to the AP-1 sequences.

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Acknowledgements

This work was supported in part by a Grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture (No. 06454468 and No. 07807154), Japan

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Tanri Shiozawa, Tsutomu Miyamoto, Hiroyasu Kashima & Ikuo Konishi

  2. Department of 2nd Anatomy, Shinshu University School of Medicine. 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Kohzo Nakayama

  3. Department of Organ Regeneration, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Toshio Nikaido

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  1. Tanri Shiozawa
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Correspondence to Tanri Shiozawa.

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Shiozawa, T., Miyamoto, T., Kashima, H. et al. Estrogen-induced proliferation of normal endometrial glandular cells is initiated by transcriptional activation of cyclin D1 via binding of c-Jun to an AP-1 sequence. Oncogene 23, 8603–8610 (2004). https://doi.org/10.1038/sj.onc.1207849

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