Identification of novel Notch target genes in T cell leukaemia

• Published in: Molecular cancer Vol. 8; no. 35; p. 35
• Main Authors: Chadwick, Nicholas, Zeef, Leo, Portillo, Virginia, Fennessy, Carl, Warrander, Fiona, Hoyle, Sarah, Buckle, Anne-Marie
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 09.06.2009; BioMed Central; BMC
• Subjects: Apoptosis; Care and treatment; CD28 Antigens - genetics; CD28 Antigens - metabolism; Down-Regulation; Flow Cytometry; Gene Expression Profiling; Genetic aspects; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Health aspects; Humans; Inhibitor of Differentiation Protein 1 - genetics; Inhibitor of Differentiation Protein 1 - metabolism; Jurkat Cells; Leukemia, T-Cell - genetics; Leukemia, T-Cell - metabolism; Lymphocytic leukemia; Oligonucleotide Array Sequence Analysis; Receptors, Notch - genetics; Receptors, Notch - metabolism; Reproducibility of Results; Risk factors; Signal Transduction - genetics; T cells; Up-Regulation; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; United Kingdom
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/1476-4598-8-35

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. 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). 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.