BACKGROUND INFORMATION: Loss of sensitivity to TGF-beta1 (transforming growth factor beta1)-induced growth arrest is an important step towards malignant transformation in human epithelial cells, and Id-1 (inhibitor of differentiation or DNA binding-1) has been associated with cell proliferation and cell-cycle progression. Here, we investigated the role of Id-1 in cellular sensitivity to TGF-beta1. RESULTS: Using an immortalized prostate epithelial cell line, NPTX cells, we suppressed Id-1 expression through antisense strategy. We found that inhibition of Id-1 expression suppressed cell proliferation and at the same time induced cellular senescence and G2/M cell-cycle arrest. In addition, inactivation of Id-1 made cells more vulnerable to TGF-beta1-induced growth arrest. The sensitization effect on TGF-beta1 was associated with up-regulation of two downstream effectors of the TGF-beta1 pathway, p21WAF1/Cip1 and p27KIP1. CONCLUSION: Our results indicate that endogenous Id-1 levels might be a crucial factor in the development of resistance to TGF-beta1-induced growth suppression in human prostate epithelial cells.
BACKGROUND INFORMATION: Loss of sensitivity to TGF-beta1 (transforming growth factor beta1)-induced growth arrest is an important step towards malignant transformation in human epithelial cells, and Id-1 (inhibitor of differentiation or DNA binding-1) has been associated with cell proliferation and cell-cycle progression. Here, we investigated the role of Id-1 in cellular sensitivity to TGF-beta1. RESULTS: Using an immortalized prostate epithelial cell line, NPTX cells, we suppressed Id-1 expression through antisense strategy. We found that inhibition of Id-1 expression suppressed cell proliferation and at the same time induced cellular senescence and G2/M cell-cycle arrest. In addition, inactivation of Id-1 made cells more vulnerable to TGF-beta1-induced growth arrest. The sensitization effect on TGF-beta1 was associated with up-regulation of two downstream effectors of the TGF-beta1 pathway, p21WAF1/Cip1 and p27KIP1. CONCLUSION: Our results indicate that endogenous Id-1 levels might be a crucial factor in the development of resistance to TGF-beta1-induced growth suppression in human prostate epithelial cells.
Authors: Hao Geng; Brooks L Rademacher; Janet Pittsenbarger; Chung-Ying Huang; Christopher T Harvey; Marie C Lafortune; Anne Myrthue; Mark Garzotto; Peter S Nelson; Tomasz M Beer; David Z Qian Journal: Cancer Res Date: 2010-04-13 Impact factor: 12.701
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