Id-1 modulates senescence and TGF-beta1 sensitivity in prostate epithelial cells.

Abstract:

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.

journal_name

Biol Cell

journal_title

Biology of the cell

authors

Di K,Ling MT,Tsao SW,Wong YC,Wang X

doi

10.1042/BC20060026

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

523-33

issue

9

eissn

0248-4900

issn

1768-322X

pii

BC20060026

journal_volume

98

pub_type

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