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Notch‐1 inhibits apoptosis in murine erythroleukemia cells and is necessary for differentiation induced by hybrid polar compounds
Author(s) -
Shelly Leslie L.,
Fuchs Chana,
Miele Lucio
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990501)73:2<164::aid-jcb3>3.0.co;2-0
Subject(s) - notch signaling pathway , apoptosis , microbiology and biotechnology , downregulation and upregulation , biology , cellular differentiation , inducer , cell , cancer research , signal transduction , gene , genetics
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. J. Cell. Biochem. 73:164–175, 1999. © 1999 Wiley‐Liss, Inc.