US EPA

1597292 

Journal Article 

Increased expression of p21Waf1/Cip1 and JNK with costimulation of prostate cancer cell activation by an siRNA Egr-1 inhibitor 

Parra, E; Gutiérrez, L; Ferreira, J 

2013 

1 

Oncology Reports
ISSN: 1021-335X
EISSN: 1791-2431 

30 

2 

911-916 

English 

23715767 

10.3892/or.2013.2503 

WOS:000321937600048 

The p21Waf1/Cip1 protein (hereafter, p21) and the c‑Jun N-terminal kinase (JNK) are two well-characterized cell modulators that play a crucial role in cell differentiation, senescence and apoptosis. Here, we report that transcription of the p21Waf1/Cip1 and JNK-1 genes is affected by inhibition of the early growth response-1 (Egr-1) in response to a small interfering RNA [siRNA)-Egr-1] in LNCaP and PC-3 prostate carcinoma cell lines. The expression levels of protein were determined by western blotting, and apoptosis was measured by propidium iodide staining and flow cytometric analysis. Inhibition of Egr-1, p21 and JNK-1 was carried out by siRNAs. LNCaP and PC-3 cells exhibited readily detectable Egr-1, JNK and p21, even in low serum medium without the addition of other exogenous agents. The expression of Egr-1, p21 and JNK was strongly increased after treatment of the cells with TPA, tumor necrosis factor-α (TNF-α) or arsenite. Suppression of Egr-1 expression by siRNA abrogated the ability of TPA to induce Egr-1 and JNK-1 activities, moderately increasing the p21 activity and abrogating the anti-apoptotic effect of Egr-1 observed in the prostate cancer cell lines. Moreover, blockade of p21 and JNK was unable to decrease the activity of Egr-1, while siRNA against p21 abrogated the pro‑apoptotic effect of p21. The results demonstrated that Egr-1 acts as a key player in prostate tumor cell growth and survival, while p21 plays a key pro‑apoptotic role in LNCaP and PC-3 prostate carcinoma cell lines. 

PC-3; LNCaP; early growth response-1; p21; c-Jun N-terminal kinase