Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells

Abstract

Background information. Loss of sensitivity to TGF-β1 (transforming growth factor β1)-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-β1. 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-β1-induced growth arrest. The sensitization effect on TGF-β1 was associated with up-regulation of two downstream effectors of the TGF-β1 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-β1-induced growth suppression in human prostate epithelial cells.