期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 113, 期 9, 页码 2845-2855出版社
WILEY
DOI: 10.1002/jcb.24159
关键词
4-HPR; MMP-9; CELL INVASION; NF-?B; BREAST CANCER
资金
- Ministry of Education, Science and Technology [2011-0026360]
- Asan Institute for Life Sciences of Seoul, Korea [2012-529]
Synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) has been reported to exhibit anti-invasive and anti-metastatic activities by suppressing the enzymatic activity of matrix metalloproteinase (MMP)-9, but the underlying mechanism remains unclear. Here, we show that 4-HPR blocks the activity of MMP-9 in two ways: by reducing phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 secretion and by suppressing cell invasion through the downregulation of MMP-9 gene transcription in MCF-7 breast cancer cells. 4-HPR inhibits the transcriptional activity of MMP-9 by reducing the DNA-binding activity of NF-?B on the MMP-9 promoter as well as by inhibiting the degradation of I?Ba, leading to cytoplasmic accumulation of NF-?B. We also found that 4-HPR inhibits invasion and MMP-9 expression in the highly metastatic breast cancer cell line MDA-MB-231. Thus, 4-HPR might be a potent anti-invasive agent that works by suppressing MMP-9 expression via the NF-?B signaling pathway. J. Cell. Biochem. 113: 28452855, 2012. (C) 2012 Wiley Periodicals, Inc.
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