Tesis doctoral de María Mena Varas
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.
Datos académicos de la tesis doctoral «Role of homeobox nkx2-3 protein in marginal-zone b-cell lymhpomagenesis using an in vivo mouse model«
- Título de la tesis: Role of homeobox nkx2-3 protein in marginal-zone b-cell lymhpomagenesis using an in vivo mouse model
- Autor: María Mena Varas
- Universidad: Navarra
- Fecha de lectura de la tesis: 21/09/2015
Dirección y tribunal
- Director de la tesis
- José ángel Martínez Climent
- Tribunal
- Presidente del tribunal: María dolores Odero de dios
- manuela Mollejo villanueva (vocal)
- césar Cobaleda hernández (vocal)
- ignacio Pérez roger (vocal)