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

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Author

  • Barbara Wegiel
  • Anders Bjartell
  • Jenny Ekberg
  • Virgil Gadaleanu
  • Cecilia Brunhoff
  • Jenny L Persson

Summary, in English

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.

Publishing year

2005

Language

English

Pages

6385-6393

Publication/Series

Oncogene

Volume

24

Issue

42

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Keywords

  • androgen receptor
  • cyclin A1
  • VEGF
  • prostate cancer
  • Rb
  • androgen

Status

Published

Research group

  • Urological cancer, Malmö
  • Pathology, Malmö

ISBN/ISSN/Other

  • ISSN: 1476-5594