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Identification of novel Notch target genes in T cell leukaemia.


ABSTRACT: BACKGROUND: Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL) cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. RESULTS: RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone) or vectors containing constitutively active forms of Notch (N1DeltaE or N3DeltaE), and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1). CONCLUSION: The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

SUBMITTER: Chadwick N 

PROVIDER: S-EPMC2698846 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Identification of novel Notch target genes in T cell leukaemia.

Chadwick Nicholas N   Zeef Leo L   Portillo Virginia V   Fennessy Carl C   Warrander Fiona F   Hoyle Sarah S   Buckle Anne-Marie AM  

Molecular cancer 20090609


<h4>Background</h4>Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL) cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat.<h4>Results</h4>RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-a  ...[more]

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