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  • Original Paper
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Androgen signaling is required for the vitamin D-mediated growth inhibition in human prostate cancer cells

Oncogene volume 23, pages 3350–3360 (2004)Cite this article

Abstract

Epidemiological data on prostate cancer incidence has suggested that vitamin D deficiency may be a risk factor for prostate cancer. The antiproliferative activity of 1α, 25-dihydroxyvitamin D3 (1,25-VD) and its analogues has been demonstrated in many prostate cancer models, yet the detailed mechanisms underlying this protective effect of vitamin D remain to be determined. Here, we demonstrate that two androgen receptor (AR)-positive prostate cancer cell lines, LNCaP and CWR22R, are more sensitive to the growth inhibitory effects of 1,25-VD compared to the AR-negative prostate cancer cell lines, PC-3 and DU 145. 1,25-VD treatment inhibited cyclin-dependent kinase 2 (cdk2) activity and induced G0/G1 arrest. Interestingly, we also found that 1,25-VD treatment induced the expression of AR, and that the onset of the G0/G1 arrest in LNCaP and CWR22R cells is correlated with the onset of increasing expression of AR. This implies that the antiproliferative actions of 1,25-VD in AR-positive prostate cancer might be mediated through AR. Furthermore, a reduction in 1,25-VD-mediated growth inhibition was observed when AR signaling was blocked by antiandrogens, AR RNA interference, or targeted disruption of AR. Taken together, our data suggest that the androgen/AR signaling plays an important role in the antiproliferative effects of 1,25-VD and restoration of androgen responsiveness by 1,25-VD might be beneficial for the treatment of hormone-refractory prostate cancer patients.

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Abbreviations

1,25-VD:

1α,25-dihydroxyvitamin D3

VDR:

vitamin D receptor

AR:

androgen receptor

Rb:

retinoblastoma

RNAi:

RNA interference

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Acknowledgements

We are grateful to Dr Lise Binderup from Leo Pharmaceutical Products for providing the 1,25-VD; Dr Franky Chan from the University of Hong Kong for CWR22R cells; and Dr Chawnshang Chang from University of Rochester for CWR22R cells expressing reduced levels of AR (CWR22R AR ↓) and AR RNAi. We also thank Loretta Collins and Karen Wolf for manuscript preparation.

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Authors and Affiliations

  1. Department of Urology, University of Rochester, Rochester, 14642, NY, USA

    Bo-Ying Bao, Huei-Ju Ting & Yi-Fen Lee

  2. Department of Chemical Engineering, University of Rochester, Rochester, 14642, NY, USA

    Bo-Ying Bao

  3. Department of Pathology, University of Rochester, Rochester, 14642, NY, USA

    Yueh-Chiang Hu

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  1. Bo-Ying Bao
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Correspondence to Yi-Fen Lee.

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Bao, BY., Hu, YC., Ting, HJ. et al. Androgen signaling is required for the vitamin D-mediated growth inhibition in human prostate cancer cells. Oncogene 23, 3350–3360 (2004). https://doi.org/10.1038/sj.onc.1207461

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