TY - JOUR
T1 - S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells
AU - Sekine, Hitoshi
AU - Chen, Na
AU - Sato, Keisuke
AU - Saiki, Yuriko
AU - Yoshino, Yuki
AU - Umetsu, Yukiko
AU - Jin, Guo
AU - Nagase, Hiroki
AU - Gu, Zhaodi
AU - Fukushige, Shinichi
AU - Sunamura, Makoto
AU - Horii, Akira
N1 - Funding Information:
We are grateful to Dr. B. L. S. Pierce (University of Maryland University College) for editorial work in the preparation of this manuscript and to Biomedical Research Core (Tohoku University School of Medicine) for technical support. This work was supported in part by Grants-in-Aid (Grant # 17015003 , 22591512 , and 23590452 ) and by the Academic Frontier Project for Private Universities: matching fund subsidy 2006–2010 from the Ministry of Education, Culture, Sports, Science and Technology of Japan , a Grant-in-Aid for Cancer Research (Grant # 18–19 ) from the Ministry of Health, Labour and Welfare of Japan , Pancreas Research Foundation of Japan , and Gonryo Medical Foundation .
PY - 2012/12/14
Y1 - 2012/12/14
N2 - S100A4, a member of the Ca2+ dependent S100 protein family, is reported to associate with metastasis through regulation of the motility and invasiveness of cancer cells. A high level of S100A4 protein has been reported in a variety of cancers, including pancreatic cancer. However, its biological role in pancreatic carcinogenesis is largely unknown. We previously reported that S100A4 is frequently overexpressed and that RNAi-mediated knockdown induces apoptosis and suppression of cell growth, motility, and invasiveness. In this study, we analyzed the effects of forced expression of S100A4 in pancreatic cancer cell lines without S100A4-upregulation. We used two cell lines without upregulation of S100A4 (PCI-35 and PCI-43) as well as two cell lines with highly upregulated S100A4 as the control (MIA PaCa-2 and PAN-07-JCK). Cells did not show acceleration of their growth and invasiveness after forced expression of S100A4, but remarkable acceleration of cell motility was observed only in PCI-35 and PCI-43. We further performed microarray analyses using PCI-35 and PCI-43 with and without forced expression of S100A4 and identified 72 and 18 genes that were 2-fold or more upregulated or downregulated, respectively, in both cell lines after forced expression of S100A4. Our results suggest that S100A4 is crucial for cell motility in pancreatic cancer and that some downstream genes may play important roles in cell motility.
AB - S100A4, a member of the Ca2+ dependent S100 protein family, is reported to associate with metastasis through regulation of the motility and invasiveness of cancer cells. A high level of S100A4 protein has been reported in a variety of cancers, including pancreatic cancer. However, its biological role in pancreatic carcinogenesis is largely unknown. We previously reported that S100A4 is frequently overexpressed and that RNAi-mediated knockdown induces apoptosis and suppression of cell growth, motility, and invasiveness. In this study, we analyzed the effects of forced expression of S100A4 in pancreatic cancer cell lines without S100A4-upregulation. We used two cell lines without upregulation of S100A4 (PCI-35 and PCI-43) as well as two cell lines with highly upregulated S100A4 as the control (MIA PaCa-2 and PAN-07-JCK). Cells did not show acceleration of their growth and invasiveness after forced expression of S100A4, but remarkable acceleration of cell motility was observed only in PCI-35 and PCI-43. We further performed microarray analyses using PCI-35 and PCI-43 with and without forced expression of S100A4 and identified 72 and 18 genes that were 2-fold or more upregulated or downregulated, respectively, in both cell lines after forced expression of S100A4. Our results suggest that S100A4 is crucial for cell motility in pancreatic cancer and that some downstream genes may play important roles in cell motility.
KW - Cell growth
KW - Microarray
KW - Motility
KW - Pancreatic cancer
KW - S100A4
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U2 - 10.1016/j.bbrc.2012.10.048
DO - 10.1016/j.bbrc.2012.10.048
M3 - Article
C2 - 23085231
AN - SCOPUS:84870721396
VL - 429
SP - 214
EP - 219
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3-4
ER -