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

Jiachi Ma, Hirozumi Sawai, Yoichi Matsuo, Nobuo Ochi, Akira Yasuda, Hiroki Takahashi, Takehiro Wakasugi, Hitoshi Funahashi, Mikinori Sato, Hiromitsu Takeyama

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)90-101
Number of pages12
JournalJournal of Surgical Research
Volume160
Issue number1
DOIs
Publication statusPublished - 01-05-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery

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