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Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells.
Oncogene. 2003 Jul 17; 22(29):4498-508.O

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-kappaB (NF-kappaB) 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 TNFalpha through inactivation of Bax and caspase 3. In addition, in the LNCaP cells expressing ectopic Id-1 protein, we also observed increased NF-kappaB 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-kappaB 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 TNFalpha-induced apoptosis. Our results strongly suggest that Id-1 may be one of the upstream regulators of NF-kappaB and activation of NF-kappaB 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.

Authors+Show Affiliations

Cancer Biology Group, Department of Anatomy, Laboratory Block, Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Hong Kong, SAR, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12881706

Citation

Ling, Ming-Tat, et al. "Id-1 Expression Promotes Cell Survival Through Activation of NF-kappaB Signalling Pathway in Prostate Cancer Cells." Oncogene, vol. 22, no. 29, 2003, pp. 4498-508.
Ling MT, Wang X, Ouyang XS, et al. Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells. Oncogene. 2003;22(29):4498-508.
Ling, M. T., Wang, X., Ouyang, X. S., Xu, K., Tsao, S. W., & Wong, Y. C. (2003). Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells. Oncogene, 22(29), 4498-508.
Ling MT, et al. Id-1 Expression Promotes Cell Survival Through Activation of NF-kappaB Signalling Pathway in Prostate Cancer Cells. Oncogene. 2003 Jul 17;22(29):4498-508. PubMed PMID: 12881706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells. AU - Ling,Ming-Tat, AU - Wang,Xianghong, AU - Ouyang,Xue-Song, AU - Xu,Kexin, AU - Tsao,Sai-Wah, AU - Wong,Yong-Chuan, PY - 2003/7/26/pubmed PY - 2003/8/20/medline PY - 2003/7/26/entrez SP - 4498 EP - 508 JF - Oncogene JO - Oncogene VL - 22 IS - 29 N2 - 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-kappaB (NF-kappaB) 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 TNFalpha through inactivation of Bax and caspase 3. In addition, in the LNCaP cells expressing ectopic Id-1 protein, we also observed increased NF-kappaB 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-kappaB 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 TNFalpha-induced apoptosis. Our results strongly suggest that Id-1 may be one of the upstream regulators of NF-kappaB and activation of NF-kappaB 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. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/12881706/Id_1_expression_promotes_cell_survival_through_activation_of_NF_kappaB_signalling_pathway_in_prostate_cancer_cells_ L2 - https://doi.org/10.1038/sj.onc.1206693 DB - PRIME DP - Unbound Medicine ER -