The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease
AUTOR(ES)
Bordeaux, Marie-Claire
FONTE
Oxford University Press
RESUMO
The RET (rearranged during transfection) proto-oncogene encodes a tyrosine kinase receptor involved in both multiple endocrine neoplasia type 2 (MEN 2), an inherited cancer syndrome, and Hirschsprung disease (HSCR), a developmental defect of enteric neurons. We report here that the expression of RET receptor induces apoptosis. This pro-apoptotic effect of RET is inhibited in the presence of its ligand glial cell line-derived neurotrophic factor (GDNF). Furthermore, we present evidence that RET induces apoptosis via its own cleavage by caspases, a phenomenon allowing the liberation/exposure of a pro-apoptotic domain of RET. In addition, we report that Hirschsprung-associated RET mutations impair GDNF control of RET pro-apoptotic activity. These results indicate that HSCR may result from apoptosis of RET-expressing enteric neuroblasts.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=306592Documentos Relacionados
- A Rare Haplotype of the RET Proto-Oncogene Is a Risk-Modifying Allele in Hirschsprung Disease
- A TaqI RFLP in the human ret proto-oncogene
- Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations.
- ASSOCIATION OF RS2435357 AND RS1800858 POLYMORPHISMS IN RET PROTO-ONCOGENE WITH HIRSCHSPRUNG DISEASE: SYSTEMATIC REVIEW AND META-ANALYSIS
- A Founding Locus within the RET Proto-Oncogene May Account for a Large Proportion of Apparently Sporadic Hirschsprung Disease and a Subset of Cases of Sporadic Medullary Thyroid Carcinoma