Notch-1 inhibits apoptosis in murine erythroleukemia cells and is necessary for differentiation induced by hybrid polar compounds
✍ Scribed by Leslie L. Shelly; Chana Fuchs; Lucio Miele
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 130 KB
- Volume
- 73
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Strikingly increased expression of notch-1 has been demonstrated in several human malignancies and pre-neoplastic lesions. However, the functional consequences of notch-1 overexpression in transformed cells remain unclear. We investigated whether endogenously expressed notch-1 controls cell fate determination in mouse erythroleukemia (MEL) cells during pharmacologically induced differentiation. We found that notch-1 expression is modulated during MEL cell differentiation. Premature downregulation of notch-1 during differentiation, by antisense S-oligonucleotides or by enforced expression of antisense notch-1 mRNA, causes MEL cells to abort the differentiation program and undergo apoptosis. Downregulation of notch-1 expression in the absence of differentiation inducer increases the likelihood of spontaneous apoptosis. We conclude that in MEL cells, endogenous notch-1 expression controls the apoptotic threshold during differentiation and growth. In these cells, notch-1 allows differentiation by preventing apoptosis of pre-committed cells. This novel function of notch-1 may play a role in regulating apoptosis susceptibility in notch-1 expressing tumor cells.