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EGR1 Addiction in Diffuse Large B-cell Lymphoma.
Kimpara, Shuichi; Lu, Li; Hoang, Nguyet M; Zhu, Fen; Bates, Paul D; Daenthanasanmak, Anusara; Zhang, Shanxiang; Yang, David T; Kelm, Amanda; Liu, Yunxia; Li, Yangguang; Rosiejka, Alexander; Kondapelli, Apoorv; Bebel, Samantha; Chen, Madelyn; Waldmann, Thomas A; Capitini, Christian M; Rui, Lixin.
Afiliación
  • Kimpara S; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Lu L; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Hoang NM; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Zhu F; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Bates PD; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Daenthanasanmak A; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Zhang S; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Yang DT; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Kelm A; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Liu Y; Lymphoid Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, Maryland.
  • Li Y; Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, Indiana.
  • Rosiejka A; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Kondapelli A; Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Bebel S; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Chen M; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Waldmann TA; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Capitini CM; Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
  • Rui L; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
Mol Cancer Res ; 19(8): 1258-1269, 2021 08.
Article en En | MEDLINE | ID: mdl-33980611
Early growth response gene (EGR1) is a transcription factor known to be a downstream effector of B-cell receptor signaling and Janus kinase 1 (JAK1) signaling in diffuse large B-cell lymphoma (DLBCL). While EGR1 is characterized as a tumor suppressor in leukemia and multiple myeloma, the role of EGR1 in lymphoma is unknown. Here we demonstrate that EGR1 is a potential oncogene that promotes cell proliferation in DLBCL. IHC analysis revealed that EGR1 expression is elevated in DLBCL compared with normal lymphoid tissues and the level of EGR1 expression is higher in activated B cell-like subtype (ABC) than germinal center B cell-like subtype (GCB). EGR1 expression is required for the survival and proliferation of DLBCL cells. Genomic analyses demonstrated that EGR1 upregulates expression of MYC and E2F pathway genes through the CBP/p300/H3K27ac/BRD4 axis while repressing expression of the type I IFN pathway genes by interaction with the corepressor NAB2. Genetic and pharmacologic inhibition of EGR1 synergizes with the BRD4 inhibitor JQ1 or the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL both in cell cultures and xenograft mouse models. Therefore, targeting oncogenic EGR1 signaling represents a potential new targeted therapeutic strategy in DLBCL, especially for the more aggressive ABC DLBCL. IMPLICATIONS: The study characterizes EGR1 as a potential oncogene that promotes cell proliferation and defines EGR1 as a new molecular target in DLBCL, the most common non-Hodgkin lymphoma.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Proteína 1 de la Respuesta de Crecimiento Precoz Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2021 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Proteína 1 de la Respuesta de Crecimiento Precoz Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: Mol Cancer Res Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2021 Tipo del documento: Article