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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 473 - 482 (10page)
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초록· 키워드
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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 -9mRNA 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 HER2overexpressed 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 HER2overexpressed MCF7 cells. Finally, HRG-induced MMP-1 and MMP-9 expression was decreased by HER3siRNA 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.
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참고문헌 (24)
참고문헌 신청
Atlas E / 2003 / Heregulin is sufficient for the promotion of tumorigenicity and metastasis of breast cancer cells in vivo / Mol Cancer Res 1 : 165 ~ 175
Bernhard EJ / 1994 / Direct evidence linking expression of matrix metalloproteinase 9 (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo ce
Chang H / 1997 / Ligands for ErbB-family receptors encoded by a neuregulin-like gene / Nature 387 : 509 ~ 512
Choi MS / 2009 / Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells / Int J Oncol 34 : 1221 ~ 1230
D'Armiento J / 1995 / Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis / Mol Cell Biol 15 :
Bernhard EJ / 1994 / Direct evidence linking expression of matrix metalloproteinase 9 (92-kDa gelatinase/collagenase) to the metastatic phenotype in transformed rat embryo ce
Chang H / 1997 / Ligands for ErbB-family receptors encoded by a neuregulin-like gene / Nature 387 : 509 ~ 512
Choi MS / 2009 / Berberine inhibits p53-dependent cell growth through induction of apoptosis of prostate cancer cells / Int J Oncol 34 : 1221 ~ 1230
D'Armiento J / 1995 / Collagenase expression in transgenic mouse skin causes hyperkeratosis and acanthosis and increases susceptibility to tumorigenesis / Mol Cell Biol 15 :
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