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Id-1 expression promotes cell survival through activation of NF-κB signalling pathway in prostate cancer cells

Oncogene volume 22, pages 4498–4508 (2003)Cite this article

Abstract

The growth-promoting effect of Id-1 (inhibitor of differentiation/DNA binding) has been demonstrated in a number of human cancers. However, the mechanisms responsible for its action are not clear. In this study, we report that in prostate cancer cells, Id-1 promotes cell survival through activation of nuclear factor-κB (NF-κB) signalling pathway. After stable expression of Id-1 protein in LNCaP cells, we found that the Id-1 transfectants showed increased resistance to apoptosis induced by TNFα through inactivation of Bax and caspase 3. In addition, in the LNCaP cells expressing ectopic Id-1 protein, we also observed increased NF-κB transactivation activity and nuclear translocation of the p65 and p50 proteins, which was accompanied by upregulation of their downstream effectors Bcl-xL and ICAM-1. These results indicate that the Id-1-induced antiapoptotic effect may be via NF-κB signalling transduction pathway in these cells. In addition, inactivation of Id-1 by its antisense oligonucleotide and retroviral construct in DU145 cells resulted in the decrease of nuclear level of p65 and p50 proteins, which was associated with increased sensitivity to TNFα-induced apoptosis. Our results strongly suggest that Id-1 may be one of the upstream regulators of NF-κB and activation of NF-κB signalling pathway may be essential for Id-1 induced cell proliferation through protection against apoptosis. Our findings also suggest a potential therapeutic strategy in which inactivation of Id-1 may lead to sensitization of prostate cancer cells to chemotherapeutic drug-induced apoptosis.

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Acknowledgements

This work was supported by RGC grants to YC Wong (HKU 7186/99 M, HKU 7314/01 M and HKU 7490/03M) and Area of Excellence Scheme (Project No. AoE/P-10/01).

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Author notes

  1. Xue-Song Ouyang

    Present address: Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School, NJ, USA

  2. Kexin Xu

    Present address: Department of Urology, People's Hospital, Beijing, China

Authors and Affiliations

  1. Department of Anatomy, Cancer Biology Group, Laboratory Block, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China

    Ming-Tat Ling, Xianghong Wang, Xue-Song Ouyang, Kexin Xu, Sai-Wah Tsao & Yong-Chuan Wong

  2. Central Laboratory of Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China

    Yong-Chuan Wong

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Correspondence to Yong-Chuan Wong.

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Ling, MT., Wang, X., Ouyang, XS. et al. Id-1 expression promotes cell survival through activation of NF-κB signalling pathway in prostate cancer cells. Oncogene 22, 4498–4508 (2003). https://doi.org/10.1038/sj.onc.1206693

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