TY - JOUR
T1 - IGF-1 Mediates PTEN Suppression and Enhances Cell Invasion and Proliferation via Activation of the IGF-1/PI3K/Akt Signaling Pathway in Pancreatic Cancer Cells
AU - Ma, Jiachi
AU - Sawai, Hirozumi
AU - Matsuo, Yoichi
AU - Ochi, Nobuo
AU - Yasuda, Akira
AU - Takahashi, Hiroki
AU - Wakasugi, Takehiro
AU - Funahashi, Hitoshi
AU - Sato, Mikinori
AU - Takeyama, Hiromitsu
PY - 2010/5/1
Y1 - 2010/5/1
N2 - Background: Type-1 insulin-like growth factor (IGF-1) up-regulates cell proliferation and invasiveness through activation of PI3K/Akt signaling pathway. IGF-1 also down-regulates the tumor suppressor chromosome 10 (PTEN). We investigated the mechanism by which IGF-1 affects cell proliferation and invasion by suppression of PTEN phosphorylation and interaction with PI3K/PTEN/Akt/NF-k{cyrillic}B signaling pathway in pancreatic cancer. Materials and Methods: The expression of IGF-1 receptor (IGF-1R) and PTEN in five pancreatic cancer cell lines was determined by RT-PCR and Western blot. Proliferation and invasion were investigated by WST-1 assay and Matrigel-double chamber assay. Pancreatic cancer cells were transfected with PTEN siRNA to investigate which signaling pathway correlates in regulation of cancer cell proliferation and invasion. Results: Five pancreatic cancer cell lines expressed PTEN and IGF-1R in mRNA and protein levels. Suppression of PTEN phosphorylation strongly enhanced cell proliferation and invasion stimulated with IGF-1 via activation of PI3K/Akt/NF-k{cyrillic}B signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-k{cyrillic}B pathway, subsequently up-regulating cell invasiveness and proliferation. Conclusions: The IGF-1/PI3K/PTEN/Akt/NF-k{cyrillic}B cascade may be a key pathway stimulating metastasis of pancreatic cancer cells. We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-k{cyrillic}B might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.
AB - Background: Type-1 insulin-like growth factor (IGF-1) up-regulates cell proliferation and invasiveness through activation of PI3K/Akt signaling pathway. IGF-1 also down-regulates the tumor suppressor chromosome 10 (PTEN). We investigated the mechanism by which IGF-1 affects cell proliferation and invasion by suppression of PTEN phosphorylation and interaction with PI3K/PTEN/Akt/NF-k{cyrillic}B signaling pathway in pancreatic cancer. Materials and Methods: The expression of IGF-1 receptor (IGF-1R) and PTEN in five pancreatic cancer cell lines was determined by RT-PCR and Western blot. Proliferation and invasion were investigated by WST-1 assay and Matrigel-double chamber assay. Pancreatic cancer cells were transfected with PTEN siRNA to investigate which signaling pathway correlates in regulation of cancer cell proliferation and invasion. Results: Five pancreatic cancer cell lines expressed PTEN and IGF-1R in mRNA and protein levels. Suppression of PTEN phosphorylation strongly enhanced cell proliferation and invasion stimulated with IGF-1 via activation of PI3K/Akt/NF-k{cyrillic}B signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-k{cyrillic}B pathway, subsequently up-regulating cell invasiveness and proliferation. Conclusions: The IGF-1/PI3K/PTEN/Akt/NF-k{cyrillic}B cascade may be a key pathway stimulating metastasis of pancreatic cancer cells. We suggest that interfering with the functions of IGF-1/PI3K/Akt/NF-k{cyrillic}B might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.
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U2 - 10.1016/j.jss.2008.08.016
DO - 10.1016/j.jss.2008.08.016
M3 - Article
C2 - 19560785
AN - SCOPUS:77950188361
SN - 0022-4804
VL - 160
SP - 90
EP - 101
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -