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.

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-small ka, CyrillicB 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-small ka, CyrillicB signaling pathway. In addition, knockdown of PTEN by siRNA transfection also enhanced activation of PI3K/Akt/NF-small ka, CyrillicB pathway, subsequently up-regulating cell invasiveness and proliferation.

CONCLUSIONS:

The IGF-1/PI3K/PTEN/Akt/NF-small ka, CyrillicB 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-small ka, CyrillicB might be a novel therapeutic approach to inhibit aggressive spread of pancreatic cancer.

• Authors: Jiachi Ma, Hirozumi Sawai, Yoichi Matsuo, Nobuo Ochi, Akira Yasuda, Hiroki Takahashi, Takehiro Wakasugi, Hitoshi Funahashi, Mikinori Sato, Hiromitsu Takeyama
• Journal: The Journal of surgical research (J Surg Res) Vol. 160 Issue 1 Pg. 90-101 (May 01 2010) ISSN: 1095-8673 [Electronic] United States
• PMID: 19560785 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies
• NF-kappa B
• RNA, Messenger
• RNA, Small Interfering
• Insulin-Like Growth Factor I
• Phosphatidylinositol 3-Kinases
• Receptor, IGF Type 1
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase
• PTEN protein, human

Topics

• Antibodies (pharmacology)
• Apoptosis (drug effects)
• Carcinoma (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Humans
• Insulin-Like Growth Factor I (immunology, metabolism)
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• PTEN Phosphohydrolase (metabolism)
• Pancreatic Neoplasms (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA Interference
• RNA, Messenger (metabolism)
• RNA, Small Interfering
• Receptor, IGF Type 1 (metabolism)
• Signal Transduction