High levels of tyrosine phosphorylated proto-ret in sporadic phenochromocytomas.
Cancer Res
; 60(5): 1365-70, 2000 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-10728700
ABSTRACT
Pheochromocytomas are tumors originating from chromaffin cells, the large majority of which are sporadic neoplasms. The genetic and molecular events determining their tumorigenesis continue to remain unknown. On the other hand, RET germ-line mutations cause the inheritance of familial tumors in multiple endocrine neoplasia (MEN)-2 diseases, which account for a minority of pheochromocytomas. We investigated the expression of the RET gene in 14 sporadic tumors harboring no activating mutations. A subset of highly RET-expressing tumors (50%) could be distinguished. They showed RET transcript, protein amounts as well as Ret-associated phosphotyrosine levels similar to those measured in MEN-2A-associated pheochromocytomas. We also determined the GDNF and GDNF family receptor alpha (GFRalpha)-1 transcript levels in tumors and in normal tissues. Whereas the GFRalpha-1 transcripts were detected at similar levels in normal tissues and in tumors, GDNF was frequently found expressed in sporadic tumors at levels several times higher than in controls. These results led us to propose the existence of an autocrine or paracrine loop leading to chronic stimulation of the Ret signaling pathway, which could participate in the pathogenesis of a number of sporadic pheochromocytomas.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Feocromocitoma
/
Proteínas Proto-Oncogênicas
/
Receptores Proteína Tirosina Quinases
/
Neoplasias das Glândulas Suprarrenais
/
Proteínas de Drosophila
/
Fatores de Crescimento Neural
Limite:
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
França