title: Decreased c-Abl activity in PC-3 and LNCaP prostate cancer cells overexpressing the early growth response-1 protein.
abstract: Early growth response-1 (Egr-1) and the non-receptor protein tyrosine kinase (c-Abl) are 2 response genes that can act as regulators of cell growth and apoptosis in response to stress. Both Egr-1 and c-Abl regulate cell proliferation and survival in different types of cancer cells. To study the effect of overexpression of EGR-1 on the activity of c-Abl in prostate cancer cells, human PC-3 and LNCaP cells were transfected with a control vector or a vector containing the murine Egr-1 cDNA and assessed for the expression of the c-Abl gene. Cells overexpressing Egr-1 were studied with respect to apoptosis (Annexin V)/DEVDase activity, Egr-1/c-Abl activation (western blotting) and cell proliferation (MTT assay). The cells were exposed to tumor necrosis factor α (TNF-α), a known inductor of Egr-1, to c-Abl inhibitor STI-571 and to small interfering RNA (siRNA)-Egr-1, respectively. The results from our studies strongly suggest that overexpression of Egr-1 decreased c-Abl activity independent of endogenous Egr-1 inhibition by siRNA-Egr-1.
authors.affiliation: Laboratory of Experimental Biomedicine, University of Tarapaca, Campus Esmeralda, Iquique, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Parra
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferreira
authors.forename: Luis
authors.initials: L
authors.lastname: Gutierrez
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001549:Benzamides / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D001549:Benzamides; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl