Revista: | Boletín médico del Hospital Infantil de México |
Base de datos: | PERIÓDICA |
Número de sistema: | 000378733 |
ISSN: | 1665-1146 |
Autores: | Méndez Maldonado, Karla1 Bonifaz, Laura C2 Baay Guzmán, Guillermina J1 Aquino Jarquín, Guillermo1 Zapata Tarrés, Marta3 Sadowinski Pine, Stanislaw4 Cabrera Muñoz, María de Lourdes4 Huerta Yépez, Sara1 |
Instituciones: | 1Hospital Infantil de México "Federico Gómez", Unidad de Investigación en Enfermedades Oncológicas, México, Distrito Federal. México 2Instituto Mexicano del Seguro Social, Centro Médico Nacional Siglo XXI, México, Distrito Federal. México 3Hospital Infantil de México "Federico Gómez", Servicio de Hemato-Oncología, México, Distrito Federal. México 4Hospital Infantil de México "Federico Gómez", Servicio de Patología, México, Distrito Federal. México |
Año: | 2014 |
Periodo: | Ene-Feb |
Volumen: | 71 |
Número: | 1 |
Paginación: | 25-35 |
País: | México |
Idioma: | Inglés |
Tipo de documento: | Artículo |
Enfoque: | Aplicado, analítico |
Resumen en inglés | Lymphomas are B and/or T cell clonal neoplasms in various states of differentiation, characteristically compromising lymph nodes. They are constituted by B and T lymphocytes that reach the node by chemokine-mediated recruitment including CXCL13. Hypoxia-inducible transcription factor (HIF-1α) plays a role in cellular adaptation to oxygen concentration changes. It also regulates expression of chemokines such as CXCL12, CCL20, and CCL5 as well as some of their receptors such as CCR7 and CXCR4. Methods: We performed in silico analysis of the CXCL13 promoter, pharmacologic modulation of HIF-1α activity and, using reporter plasmids, site-directed mutation and DNA-protein interaction analysis we analyzed the relation between HIF-1α activity and CXCL13 expression. Moreover, we did tissue microarray and immunohistochemistry to see the expression of HIF-1α and CXCL13. Results: This study detected three possible HIF-1α binding sites suggesting that this chemokine may be regulated by the CXCL13 transcription factor. We showed that CXCL13 expression is directly dependent, whereby an increase in HIF-1α activity increases CXCL13 expression and decreased HIF-1α activity in turn decreases CXCL13 expression. We proved that HIF-1α transcriptionally regulates the expression of CXCL13 in a direct manner. We established that HIF-1α and CXCL13 are greatly overexpressed in the most aggressive pediatric lymphomas. Conclusions: For the first time, this study showed that HIF-1α directly regulates transcriptional CXCL13 and that both proteins are overexpressed in the most aggressive forms of pediatric lymphoma. This suggests that they may play a significant role in the pathogenesis of pediatric non-Hodgkin's lymphoma |
Disciplinas: | Medicina |
Palabras clave: | Oncología, Pediatría, Biología celular, HIF1A, CXCL13, Linfoma no Hodgkin, Microarreglos, Tejidos |
Keyword: | Medicine, Oncology, Pediatrics, Cell biology, HIF1A, CXCL13, Non-Hodgkin lymphoma, Microarrays, Tissues |
Texto completo: | Texto completo (Ver HTML) |