A role for cyclin A1 in mediating the autocrine expression of vascular endothelial growth factor in prostate cancer.
Author
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.
Department/s
Publishing year
2005
Language
English
Pages
6385-6393
Publication/Series
Oncogene
Volume
24
Issue
42
Links
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