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Metalloprotease‐disintegrin ADAM12 expression is regulated by Notch signaling via microRNA‐29b
Author(s) -
Li Hui,
Muggy Sara Duhachek,
Solomon Emilia,
Sun Danqiong,
Zolkiewska Anna
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.514.2
Metalloprotease‐disintegrin ADAM12 is overexpressed and frequently mutated in breast cancer. We have found that ADAM12 expression in cultured mammalian cells is up‐regulated by Notch signals. Expression of a constitutively active form of Notch1 in murine fibroblasts, myoblasts, or mammary epithelial cells, or activation of the endogenous Notch signaling by co‐culture with ligand‐expressing cells, increases ADAM12 protein and mRNA levels. ADAM12 expression by Notch requires new transcription and is activated in a CSL‐ and NFκB‐dependent manner. The regulation of ADAM12 expression by Notch involves down‐regulation of microRNA‐29b and increased stability of ADAM12 mRNA. In human cells, Notch up‐regulates the expression of the long form, but not the short form of ADAM12 containing a divergent 3′‐untranslated mRNA region. These studies uncover a novel paradigm in Notch signaling and establish ADAM12 as a Notch‐related gene. This work was supported by NIH grant CA151065 and Innovative Research Award from Terry C. Johnson Center for Basic Cancer Research at KSU.