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Protein Kinase C-dependent Regulation of NAG-1/Placental Bone Morphogenic Protein/MlC-1 Expression in LNCaP Prostate Carcinoma Cells.
- Source :
-
Journal of Biological Chemistry . 5/13/2005, Vol. 280 Issue 19, p18636-18642. 7p. 4 Graphs. - Publication Year :
- 2005
-
Abstract
- NAG-1 (nonsteroidal anti-inflammatory drug-activated gene), a member of the transforming growth factor β superfamily, is involved in cellular processes such as inflammation, apoptosis/survival, and tumorigenesis and is regulated by p53, Sp1, and Egr-1. In the current study, the regulation of NAG-1 expression in LNCaP human prostate carcinoma cells by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was examined. TPA treatment increased NAG-1 protein and mRNA levels in a time- and concentration-dependent manner as well as NF-κB binding/transcriptional activity in LNCaP cells. Pretreatment with protein kinase C (PKC) inhibitor blocked the TPA-induced increase in NAG-1 protein levels and NF-κB binding/transcriptional activity, whereas an inhibition of p38, JNK, MEK activity had no effect on TPA-induced NAG-1 levels and NF-κB transcriptional activity. Expression of constitutively active PKCs induced an increase in NF-κB transcriptional activity and NAG-1 protein levels in LNCaP cells. The expression of NF-κB p65 induced NAG-1 promoter activity, and chromatin immunoprecipitation assay for p65 showed that NF-κB binds the NAG-1 promoter in LNCaP cells. Inhibition of TPA-induced NAG-1 expression by NAG-1 short interfering RNA blocked TPA-induced apoptosis in LNCaP cells, suggesting induction of NAG-1 negatively affects LNCaP cell survival. These results demonstrate that NAG-1 expression is up-regulated by TPA in LNCaP cells through a PKC-dependent pathway involving the activation of NF-κB. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 280
- Issue :
- 19
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17141111
- Full Text :
- https://doi.org/10.1074/jbc.M414613200