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A functional comparison between the HER2(high)/HER3 and the HER2l(ow/)HER3 dimers on heregulin-beta 1-induced MMP-1 and MMP-9 expression in breast cancer cells

Title
A functional comparison between the HER2(high)/HER3 and the HER2l(ow/)HER3 dimers on heregulin-beta 1-induced MMP-1 and MMP-9 expression in breast cancer cells
Other Titles
HER3 and the HER2l(ow
Author
신인철
Keywords
Breast neoplasms; HER2 protein; Heregulin-β1; Human; Matix metalloproteinase 1; Matrix metalloproteinase 9; Mitogen-activated protein kinase 1; Neoplasm metastasis
Issue Date
2012-08
Publisher
Korean Society for Biochemistry and Molecular Biongy
Citation
Experimental & Molecular Medicine, Vol.44 No.8 [2012], pages 473?482
Abstract
Overexpression of HER2 correlates with more aggressive tumors and increased resistance to cancer chemotherapy. However, a functional comparison between the HER2high/HER3 and the HER2low/HER3 dimers on tumor metastasis has not been conducted. Herein we examined the regulation mechanism of heregulin-β1 (HRG)-induced MMP-1 and -9 expression in breast cancer cell lines. Our results showed that the basal levels of MMP-1 and -9 mRNA and protein expression were increased by HRG treatment. In addition, HRG-induced MMP-1 and -9 expression was significantly decreased by MEK1/2 inhibitor, U0126 but not by phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294002. To confirm the role of MEK/ERK pathway on HRG-induced MMP-1 and -9 expression, MCF7 cells were transfected with constitutively active adenoviral-MEK (CA-MEK). The level of MMP-1 and -9 expressions was increased by CA-MEK. MMP-1 and -9 mRNA and protein expressions in response to HRG were higher in HER2 overexpressed cells than in vector alone. The phosphorylation of HER2, HER3, ERK, Akt, and JNK were also significantly increased in HER2 overexpressed MCF7 cells compared with vector alone. HRG-induced MMP-1 and -9 expressions were significantly decreased by lapatinib, which inhibits HER1 and HER2 activity, in both vector alone and HER2 overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3 siRNA overexpression. Taken together, we suggested that HRG-induced MMP-1 and MMP-9 expression is mediated through HER3 dependent pathway and highly expressed HER2 may be associated with more aggressive metastasis than the low expressed HER2 in breast cancer cells.
URI
http://www.nature.com/articles/emm201254http://hdl.handle.net/20.500.11754/40986
ISSN
1226-3613; 2092-6413
DOI
10.3858/emm.2012.44.8.054
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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