This report describes a model of glioblastoma (an aggressive cancer originating in astrocytes) with elevated NR2E1. NR2E1 is a nuclear orphan receptor also known as TLX (not to be confused with human genes TLX1/2/3). In mammals, NR2E1 is expressed in both neural stem cells and in glioblastoma stem cells.
There is a single high-ranking ortholog of NR2E1 in Drosophila, tll. A large number of alleles have been generated for tll, including various types of loss and gain of function alleles, RNAi targeting constructs, overexpression constructs, and alleles generated by insertional mutagenesis.
The wild-type human gene NR2E1 has been introduced into flies.
Ubiquitous overexpression of tll in the brain causes tumors in the larval and adult brains which are composed largely of neural stem cells (NSCs). The same tumorous phenotype is seen when tll or the human ortholog Hsap\NR2E1 is expressed only in the intermediate neural progenitor (INP) cells, which are a tumor-susceptible cell type and the origin of tll and Hsap\NR2E1-induced tumors in Drosophila. Co-expression of tll with ase (a proneural gene repressed by tll) prevented tumor growth.
[updated Apr. 2020 by FlyBase; FBrf0222196]
Malignant gliomas are histologically heterogeneous and invasive tumors that are derived from glia. Typically, they contain both neoplastic and stromal tissues, which contribute to their histologic heterogeneity and variable outcome. (From Wen and Kesari 2008, pubmed:18669428.)
In patient tissue and mouse models, astrocyte-like neural stem cells that carry driver mutations migrate from the subventricular zone and lead to the development of high-grade malignant gliomas in distant brain regions. (Adapted from Lee et al. 2018, pubmed:30069053.)
One to one: 1 human gene to 1 Drosophila gene.
Single, high-scoring ortholog of Hsap\HR2E1.
