title: Association of increased levels of TGF-β1 and p14ARF in prostate carcinoma cell lines overexpressing Egr-1.
abstract: The present study examined the effect of the overexpression of early growth response gene (Egr-1) on transforming growth factor β-1 (TGF-β1) and p14ARF levels, in PC-3 and LNCaP prostate carcinoma cell lines. Amplification of EGR-1, TGF-β1 and p14ARF were observed in the two cell lines treated with different stimuli and resulted in a corresponding mRNA and protein expression. The downregulation of TGF-β1 and the attenuation of p14ARF expression by siRNA against Egr-1 predominantly suggested that TGF-β1 and p14ARF may be regulated by the transcription factor EGR-1. A marginal attenuation of cell growth in PC-3 and LNCaP prostate carcinoma cell lines overexpressing p14ARF was observed. Cells transfected with Egr-1 wild-type were able to grow and avoid cell cycle arrest and apoptosis in the presence or absence of p14ARF. In addition, EGR-1 stimulated the expression of TGF β-l as well as the accumulation of the p14ARF proteins. The results suggested that TGF-β1 and p14ARF activities in the presence of EGR-1 overexpression can exist independently of the presence of cells carrying a mutant p53 (PC-3 cells) or cells carrying a wild‑type p53 (LNCaP cells). Thus, the effect of EGR-1 on the growth of prostate carcinoma cells may occur through multiple mechanisms, but be independent of p53 expression control.
authors.affiliation: Laboratory of Experimental Biomedicine, University of Tarapaca, Campus Esmeralda, Iquique, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Parra
authors.affiliation: Faculty of Sciences, Arturo Prat University, Iquique, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Gutiérrez
authors.affiliation: Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Independencia, Santiago, Chile.
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C508960:TGFB1 protein, human; C495901:TP53 protein, human; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53