2024-03-29T07:02:54Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/249322016-02-16T07:19:26Zcom_10261_79com_10261_1col_10261_332
A role for stroma-derived annexin A1 as mediator in the control of genetic susceptibility to T-cell lymphoblastic malignancies through prostaglandin E2 secretion
Santos, Javier
González-Sánchez, Laura
Matabuena-deYzaguirre, María
Villa-Morales, María
Cozar, Patricia
López-Nieva, Pilar
Fernández-Navarro, Pablo
Díaz-Muñoz, Manuel D.
Guenet, Jean-Louis
Montagutelli, Xavier
Fernández-Piqueras, José
European Commission
Ministerio de Educación y Ciencia (España)
Thymic-lymphomas
gamma-irradiation
low-penetrance-genes
thymus-stroma
Annexin A1
Cancer susceptibility is essentially attributable to multiple low-penetrance genes. Using
interspecific consomic and congenic mice between the tumour-resistant SEG/Pas and
the tumour-sensitive C57BL/6J strains, a region on chromosome 19 involved in the
genetic resistance to γ-irradiation-induced T-cell lymphomas (Tlyr1) has been
identified. Through the development of non-overlapping sub-congenic strains, it has
been further demonstrated that Anxa1 may be a candidate resistance gene on the basis of
its differential expression in thymus stroma cells after γ-radiation exposure. In addition,
thymus-stroma cells of thymic lymphomas exhibited a significant reduction in the
expression levels of Anxa1. Interestingly, the activity of Anxa1 relies on prostaglandin
E2 (PGE2) induction that brings about apoptosis in thymocytes. In fact, in vitro
transfection experiments revealed that PGE2 production was enhanced when HEK 293
cells were transfected with full-length cDNAs of Anxa1, with PGE2 production in the
cells transfected with the allele of the resistant strain (Anxa1Tyr) being higher than that
in cells transfected with the allele of the susceptible strain (Anxa1Phe). Furthermore, the
presence of this compound in the medium induced apoptosis of immature
CD4+CD8+CD3low cells in a dose-dependent manner. These results improve our
knowledge of the molecular mechanisms triggering T-cell lymphoblastic lymphoma
development, while highlighting the relevance of the stroma in controlling genetic
susceptibility, and the use of PGE2 as a new therapeutic approach in T-cell
haematogical malignancies.
2010-06-01T13:53:07Z
2010-06-01T13:53:07Z
2009-03-15
artículo
Cancer Research 69(6):2577-87(2009)
0008-5472
http://hdl.handle.net/10261/24932
10.1158/0008-5472.CAN-08-1821
http://dx.doi.org/10.13039/501100000780
eng
http://dx.doi.org/10.1158/0008-5472.CAN-08-1821
openAccess
American Association for Cancer Research