Notch signalling antibodies and the jagged edge of cancer research
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An extensive antibody catalog exists for the Notch signaling pathway. Notch proteins play an essential role in embryonic development and cell-signaling, with antibody studies showing them to be critical to apoptosis, vasculogenesis, hematopoiesis, myogenesis, morphogenesis and T-cell development. The Notch pathway has also been implicated in various types of cancer.
Antibody studies have identified Notch proteins to have a dual role, acting as both transcription factors, and as membrane receptors for Delta and Jagged ligands. Recently, scientists working with Notch signaling antibodies identified one of these ligands, Jagged2, as a promoter of metastasis in lung cancer. Jagged2 binds to the Notch2 receptor.
Ligand binding occurs at the Notch extracellular domain, resulting in a series of cleavages at the cytoplasmic domain. The Notch protein then translocates to the nucleus, triggering expression of Notch-responsive genes. Antibody research has indicated Notch signaling may be bi-directional, triggering events in the Jagged and Delta-expressing cells.
In a recent study using a mouse model for non-small cell (NSC) lung cancer, Kurie, Yang et al found that Jagged2/Notch2 binding can lead to silencing of miR-200. miR-200 is a microRNA thought to inhibit metastasis at the epithelial-to-mesenchymal transition stage.
The researchers first identified and isolated pro-metastatic NSC lung cancer cells, using CD133 marker antibodies. CD133 is virtually absent from primary lung tumors, but present in over 80% of the cell population of metastatic lesions. Over 50% of mice injected with CD133(+) cells developed metastatic cancer, compared to less than 20% of CD133(-) injected controls.
The CD133(+) cells showed marked overexpression of Notch ligands. In knock-down studies, cells depleted of Jagged2 failed to metastasize, while Jagged1 depletion had no effect. Further antibody experiments suggested Jagged2 inhibits miR-200 expression by regulating GATA3 expression. Studies have shown GATA3 and miR-200 counter-inhibit each other, and overexpression of GATA3 lowered miR-200 levels.
We at Novus Biologicals have an extensive antibody database covering all areas of the Notch signaling pathway. |
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The Article is written by www.novusbio.com providing Antibody Database and Antibody Suppliers. Visit http://www.novusbio.com for more information on www.novusbio.com Products and Services___________________________Copyright information This article is free for reproduction but must be reproduced in its entirety, including live links and this copyright statement must be included. Visit www.novusbio.com for more services!
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By :
Brigette Federico
Submitted
2011-06-26 09:26:41 |
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