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A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer

Oncogene volume 24, pages 6385–6393 (2005)Cite this article

Abstract

Elevated levels of cyclin A1 expression have been implicated in acute myeloid leukemia and in male germ cell tumors. However, a role of cyclin A1 in tumorigenesis of prostate cancer has not been reported. In the present study, expression of cyclin A1 in patients with prostate cancer and a role of cyclin A1 in mediating expression of vascular endothelial growth factor (VEGF) were investigated. Cyclin A1 was highly expressed in aggressive tumors and was significantly correlated with VEGF expression in 96 patients with prostate cancer. Treatment of LNCaP cells with R1881, a synthetic androgen resulted in increased cyclin A1 expression. Induction of cyclin A1 expression in LNCaP cells led to an increase in VEGF expression and this effect was manifested upon the R1881 treatment. Cyclin A1 failed to mediate VEGF activation in DU-145 cells lacking a functional Rb and an androgen receptor (AR). Although AR expression was induced into DU-145 cells, cyclin A1 was unable to mediate VEGF expression. However, induced coexpression of cyclin A1, Rb and AR in DU-145 cells in the presence of R1881 greatly promoted VEGF promoter activity. This suggests that cyclin A1 mediates VEGF expression in cooperation with Rb- and androgen-dependent pathways in prostate cancer.

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Acknowledgements

We thank Ms Elise Nilsson for the excellent technical assistant and Caroline Holm for showing several experimental analysis, and Drs Nisthman Dizeyi, Dieter Marme, Seema Rosqvist, Yvonne Giwereman, Jiri Bartek, Albert Brinkmann, James De-Caprio, and Göran Landberg for helpful discussions. This work was supported by the Swedish Cancer Society (Projects No. 4294 and 4573-B02-02XBB), The Swedish National Research Council, MAS Cancer Foundation, Swedish Royal Physiographic Society in Lund, Crafoords Foundation and MAS Foundation; The Foundation for Urology Research in Malmö, The Thulefjord Foundation and The Per, Lise, Niels, and Bredberg Foundations.

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  1. Barbara Wegiel

    Present address: Department of Surgery, Immunobiology Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA

Authors and Affiliations

  1. Department of Laboratory Medicine, Division of Pathology, Lund University, University Hospital, Malmö, 20502, Sweden

    Barbara Wegiel, Jenny Ekberg, Virgil Gadaleanu, Cecilia Brunhoff & Jenny Liao Persson

  2. Department of Urology, Lund University, University Hospital, Malmö, Sweden

    Barbara Wegiel & Anders Bjartell

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  1. Barbara Wegiel
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Correspondence to Jenny Liao Persson.

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Wegiel, B., Bjartell, A., Ekberg, J. et al. A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer. Oncogene 24, 6385–6393 (2005). https://doi.org/10.1038/sj.onc.1208795

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