Matrix metalloproteinase-1 expression can be upregulated through mitogen-activated protein kinase pathway under the influence of human epidermal growth factor receptor 2 synergized with estrogen receptor.
In our previous work, Ets-1 upregulates human epidermal growth factor receptor 2 (HER2) induced matrix metalloproteinase 1 (MMP-1) expression. Based on the above knowledge and result, we hypothesized that estrogen receptor (ER) and its signaling pathway may affect MMP-1 expression under the influence of HER2. In addition, we investigated how the HER2 pathway cross-talk with the ER signaling pathway in genomic and nongenomic action of ER using reverse transcription-PCR, Western blot analysis, and ELISA assay. The results showed that ER-alpha expression increased MMP-1 expression under the presence of HER2. These upregulatory effects were mediated mainly by mitogen-activated protein kinase pathway and were reversed by downregulation of HER2 and/or ER. Activator protein DNA binding activity was involved in the MMP-1 expression. In summary, our results showed that ER can upregulate MMP-1 expression under the influence of HER2 in MCF-7 cells. In addition, this upregulatory effect was found to be mediated by mitogen-activated protein kinase pathway. MMP-1 might be an assigned target in interaction between ER and HER2.
Jung
Hae Hyun
HH
Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Park
Yeon Hee
YH
Jun
Hyun Jung
HJ
Kong
Jeehyun
J
Kim
Jeong Hoon
JH
Kim
Jung A
JA
Yun
Jina
J
Sun
Jong Mu
JM
Won
Young Woong
YW
Lee
Soohyeon
S
Kim
Seung Tae
ST
Ahn
Jin Seok
JS
Im
Young-Hyuck
YH
D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
D011960:Receptors, Estrogen; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1