Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model
NKX2 homeobox family proteins play a role in cancer development. Molecular cloning of a translocation t(10;14)(q24;q32) from a marginal-zone B-cell lymphoma revealed NKX2-3 as an IGH partner gene, leading to increased NKX2-3 expression with respect to B lymphocytes. NKX2-3 overexpression was also de...
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| Format: | info:eu-repo/semantics/doctoralThesis |
| Language: | eng |
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2016
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| Online Access: | https://hdl.handle.net/10171/39773 |
| _version_ | 1793400590476247040 |
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| author | Mena-Varas, M. (María) Martinez-Climent, J.A. (José Ángel) Robles, E.F. (Eloy Francisco) |
| author_facet | Mena-Varas, M. (María) Martinez-Climent, J.A. (José Ángel) Robles, E.F. (Eloy Francisco) |
| author_sort | Mena-Varas, M. (María) |
| collection | DSpace |
| description | NKX2 homeobox family proteins play a role in cancer development. Molecular cloning of a translocation t(10;14)(q24;q32) from a marginal-zone B-cell lymphoma revealed NKX2-3 as an IGH partner gene, leading to increased NKX2-3 expression with respect to B lymphocytes. NKX2-3 overexpression was also detected in tumor cells from a subset of patients with extranodal and splenic marginal-zone lymphomas, but not with other mature B-cell malignancies. While Nkx2-3 deficient mice exhibited atrophic spleens with absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells showed progressive splenomegaly with marginal-zone expansion, and eventually developed tumors faithfully recapitulating the phenotype, cellular and molecular biology of human marginal-zone lymphomas. Mechanistically, NKX2-3 induced constitutive B-cell receptor (BCR) signaling by phosphorylating Lyn and Syk kinases. These molecules enhanced proliferation and eventually acquiring genomic rearrangements that triggered NF-κB and PI3K-AKT pathways to drive malignant transformation. This study implicates oncogenic NKX2-3 in marginal-zone lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human lymphoma. |
| format | info:eu-repo/semantics/doctoralThesis |
| id | oai:dadun.unav.edu:10171-39773 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2016 |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-397732020-03-03T13:18:44Z Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model Mena-Varas, M. (María) Martinez-Climent, J.A. (José Ángel) Robles, E.F. (Eloy Francisco) Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud NKX2 homeobox family proteins play a role in cancer development. Molecular cloning of a translocation t(10;14)(q24;q32) from a marginal-zone B-cell lymphoma revealed NKX2-3 as an IGH partner gene, leading to increased NKX2-3 expression with respect to B lymphocytes. NKX2-3 overexpression was also detected in tumor cells from a subset of patients with extranodal and splenic marginal-zone lymphomas, but not with other mature B-cell malignancies. While Nkx2-3 deficient mice exhibited atrophic spleens with absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells showed progressive splenomegaly with marginal-zone expansion, and eventually developed tumors faithfully recapitulating the phenotype, cellular and molecular biology of human marginal-zone lymphomas. Mechanistically, NKX2-3 induced constitutive B-cell receptor (BCR) signaling by phosphorylating Lyn and Syk kinases. These molecules enhanced proliferation and eventually acquiring genomic rearrangements that triggered NF-κB and PI3K-AKT pathways to drive malignant transformation. This study implicates oncogenic NKX2-3 in marginal-zone lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human lymphoma. 2016-01-21T11:24:45Z 2016-01-21T11:24:45Z 2016 2015-09-21 info:eu-repo/semantics/doctoralThesis https://hdl.handle.net/10171/39773 eng info:eu-repo/semantics/openAccess application/pdf |
| spellingShingle | Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud Mena-Varas, M. (María) Martinez-Climent, J.A. (José Ángel) Robles, E.F. (Eloy Francisco) Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_full | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_fullStr | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_full_unstemmed | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_short | Role of homeobox NKX2-3 protein in marginal-zone B-cell lymphomagenesis using an in vivo mouse model |
| title_sort | role of homeobox nkx2-3 protein in marginal-zone b-cell lymphomagenesis using an in vivo mouse model |
| topic | Biología molecular Genética molecular Materias Investigacion::Ciencias de la Salud |
| url | https://hdl.handle.net/10171/39773 |
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