Carcinogenesis Advance Access published online on December 19, 2003
Carcinogenesis, doi:10.1093/carcin/bgh047
© 2003 by Oxford University Press
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CANCER BIOLOGY
1 Cancer Biology Group, Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China
* Corresponding author. E-mail: ycwong{at}hkuc.hku.hk.
Received 29 July 2003
; revised 12 November 2003
; accepted 30 November 2003
The failure of prostate cancer treatment is largely due to the development of androgen independence, since the androgen depletion therapy remains the front-line option for this cancer. Previously, we reported that over-expression of the helix-loop-helix protein Id-1 was associated with progression of prostate cancer and ectopic expression of Id-1 induced serum independent proliferation in prostate cancer cells. In the present study, we investigated if exogenous Id-1 expression in the androgen sensitive LNCaP cells had any effect on androgen dependent cell growth and studied the molecular mechanisms involved. Using stable Id-1 transfectants, we found that expression of Id-1 was able to reduce androgen-stimulated growth and S phase fraction of the cell cycle in LNCaP cells, indicating that Id-1 may be involved in the development of androgen independence in these cells. The Id-1-induced androgen independent prostate cancer cell growth was correlated with upregulation of EGF-R (epidermal growth factor-receptor) and PSA (prostate specific antigen) expression, as confirmed by Western blotting analysis and luciferase assays. In contrast, down-regulation of Id-1 in androgen independent DU145 cells by its antisense oligonucleotides resulted in suppression of EGF-R expression at both transcriptional and protein levels. In addition, the results from immunohistochemistry study showed that Id-1 expression was significantly elevated in hormone refractory prostate cancer tissues when compared with the hormone dependent tumours. Our results suggest that upregulation of Id-1 in prostate cancer cells may be one of the mechanisms responsible for developing androgen independence and this process may be regulated through induction of EGF-R expression. Inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of androgen independent prostate cancer cell growth.
Id-1, prostate cancer, androgen independence, EGF-R
Id-1 expression induces androgen independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R)
2 Cancer Biology Group, Department of Surgery, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China
3 Cancer Biology Group, Department of Anatomy, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China; Central Laboratory of Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China
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