title: Increased expression of p21Waf1/Cip1 and JNK with costimulation of prostate cancer cell activation by an siRNA Egr-1 inhibitor.
abstract: 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.
authors.affiliation: Laboratory of Experimental Biomedicine, University of Tarapaca, Campus Esmeralda, Iquique, Chile. eparra@uta.cl
authors.forename: Eduardo
authors.initials: E
authors.lastname: Parra
authors.forename: Luis
authors.initials: L
authors.lastname: Gutiérrez
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics*; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D034741:RNA, Small Interfering; D048031:JNK Mitogen-Activated Protein Kinases