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Pathogenetic implications of early growth response 1 in Ewing sarcoma.
Noh, Byeong-Joo; Jung, Woon-Won; Kim, Hyun-Sook; Park, Yong-Koo.
Afiliación
  • Noh BJ; Department of Pathology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea.
  • Jung WW; Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Chungbuk, South Korea.
  • Kim HS; Department of Biomedical Laboratory Science, College of Health Science, Cheongju University, Chungbuk, South Korea.
  • Park YK; Department of Pathology, School of Medicine, Kyung Hee University, Seoul, South Korea. Electronic address: ykpark0204@gmail.com.
Pathology ; 51(6): 605-609, 2019 Oct.
Article en En | MEDLINE | ID: mdl-31466866
Ewing sarcoma (ES) is the second most common primary malignant bone tumour, mainly occurs in children and adolescents, and has an overwhelming mortality. Despite extensive studies, few effective oncogenic signals have been described. Therefore, it is crucial to exploit novel pathognomonic factors and targetable biomarkers for ES patients. Based on previous studies, we speculate that insulin-like growth factor 1 receptor (IGF1R), which is upregulated by early growth response 1 (EGR1), may play a pivotal role in strengthening the downward transmission of IGF1 cascades. Therefore, in this study, we concentrated on determining the pathogenetic contribution of EGR1 in diverse ES cells. This report is the first to study the pathogenic role of EGR1 in ES. ES cells were cultured and transfected with Stealth RNAi human EGR1 small interfering RNA (siRNA) or negative control. Cell proliferation and invasion potential were measured. mRNA and protein expression of EGR1, IGF1R, and EWS-FLI1 also were assessed. In all EGR1 siRNA-transfected cells (SK-ES-1, RD-ES, and HS863.T), cell proliferation and invasive potential decreased significantly in EGR1 siRNA-transfected ES cells. mRNA and protein expression for EGR1, IGF1R, and EWS-FLI1 were also significantly reduced. In conclusion, EGR1 upregulated IGF1R expression and enhanced the expression of the oncogenic fusion protein EWS-FLI1. The EWS-FLI1/EGR1/IGF1R cascade combined with the previously confirmed pathways can form a speculative circuit, implicating positive feedback for tumourigenesis in ES. Therefore, EGR1 inhibitors are expected to be useful for the treatment of ES by preventing oncogenic IGF1/IGF1R expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma de Ewing / Neoplasias Óseas / Proteína 1 de la Respuesta de Crecimiento Precoz Límite: Female / Humans / Male Idioma: En Revista: Pathology Año: 2019 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sarcoma de Ewing / Neoplasias Óseas / Proteína 1 de la Respuesta de Crecimiento Precoz Límite: Female / Humans / Male Idioma: En Revista: Pathology Año: 2019 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido