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Citation
Read, R.D., Goodfellow, P.J., Mardis, E.R., Novak, N., Armstrong, J.R., Cagan, R.L. (2005). A Drosophila model of multiple endocrine neoplasia type 2.  Genetics 171(3): 1057--1081.
FlyBase ID
FBrf0190765
Publication Type
Research paper
Abstract

Dominant mutations in the Ret receptor tyrosine kinase lead to the familial cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Mammalian tissue culture studies suggest that RetMEN2 mutations significantly alter Ret-signaling properties, but the precise mechanisms by which RetMEN2 promotes tumorigenesis remain poorly understood. To determine the signal transduction pathways required for RetMEN2 activity, we analyzed analogous mutations in the Drosophila Ret ortholog dRet. Overexpressed dRetMEN2 isoforms targeted to the developing retina led to aberrant cell proliferation, inappropriate cell fate specification, and excessive Ras pathway activation. Genetic analysis indicated that dRetMEN2 acts through the Ras-ERK, Src, and Jun kinase pathways. A genetic screen for mutations that dominantly suppress or enhance dRetMEN2 phenotypes identified new genes that are required for the phenotypic outcomes of dRetMEN2 activity. Finally, we identified human orthologs for many of these genes and examined their status in human tumors. Two of these loci showed loss of heterozygosity (LOH) within both sporadic and MEN2-associated pheochromocytomas, suggesting that they may contribute to Ret-dependent oncogenesis.

PubMed ID
PubMed Central ID
PMC1456812 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genetics
    Title
    Genetics
    Publication Year
    1916-
    ISBN/ISSN
    0016-6731
    Data From Reference
    Aberrations (42)
    Alleles (151)
    Genes (100)
    Human Disease Models (2)
    Natural transposons (1)
    Insertions (34)
    Experimental Tools (1)
    Transgenic Constructs (4)