1. Smad7 acts as a negative regulator of the epidermal growth factor (EGF) signaling pathway in breast cancer cells
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Kim, Sangmin, Han, Jeonghun, Lee, Se Kyung, Koo, Minyoung, Cho, Dong Hui, Bae, Soo Youn, Choi, Min-Young, Kim, Jee Soo, Kim, Jung-Han, Choe, Jun-Ho, Yang, Jung-Hyun, Nam, Seok Jin, and Lee, Jeong Eon
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BREAST cancer , *CANCER cells , *EPIDERMAL growth factor , *CELLULAR signal transduction , *GENE expression , *PHOSPHORYLATION - Abstract
Abstract: Although it has been suggested that smad7 blocks downstream signaling of TGF-β, the role of smad7 in the EGF signaling pathway has not been fully elucidated. We determined the effect of smad7 on EGF-induced MMP-9 expression in SKBR3 breast cancer cells. The expression of smad7 and MMP-9 was increased by EGF or TGF-β1, respectively, and further increased by EGF and TGF-β1 co-treatment. EGF induced the phosphorylation of EGFR, smad3, ERK, and JNK, and MMP-9 expression was decreased by the EGFR inhibitor, AG1478. In addition, EGF-induced MMP-9 expression was inhibited by UO126 (a MEK1/2 inhibitor) or SIS3 (a smad3 inhibitor), but not by SP600125 (a JNK inhibitor). Interestingly, EGF-induced smad3 phosphorylation was completely blocked by smad7 over-expression, but not the phosphorylation of ERK and JNK. EGF- or TGF-β1-induced MMP-9 expression was completely decreased by adenoviral-smad7 (Ad-smad7) over-expression. We also investigated the role of smad3 on EGF-induced MMP-9 expression and showed that EGF-induced MMP-9 expression was decreased by smad3 siRNA transfection, whereas EGF-induced MMP-9 expression was further increased by smad3 over-expression, as expected. This study showed that EGF-induced smad3 phosphorylation mediates the induction of MMP-9, whereas smad7 inhibits TGF-β1 as well as the EGF signaling pathway in SKBR3 cells. [Copyright &y& Elsevier]
- Published
- 2012
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