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PTEN regulate angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells

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Abstract

Phosphoinositide 3-kinase (PI3K) pathway exerts its effects through Akt, its downstream target molecule, and thereby regulates various cell functions including cell proliferation, cell transformation, apoptosis, tumor growth, and angiogenesis. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been implicated in regulating cell survival signaling through the PI3K/Akt pathway. However, the mechanism by PI3K/PTEN signaling regulates angiogenesis and tumor growth in vivo remains to be elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in tumor angiogenesis. The effect of PTEN on VEGF-mediated signal in pancreatic cancer is unknown. This study aimed to determine the effect of PTEN on both the expression of VEGF and angiogenesis. Toward that end, we used the siRNA knockdown method to specifically define the role of PTEN in the expression of VEGF and angiogenesis. We found that siRNA-mediated inhibition of PTEN gene expression in pancreatic cancer cells increase their VEGF secretion, up-modulated the proliferation, and migration of co-cultured vascular endothelial cell and enhanced tubule formation by HUVEC. In addition, PTEN modulated VEGF-mediated signaling and affected tumor angiogenesis through PI3K/Akt/VEGF/eNOS pathway.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Science, Kawasumi 1, Mizuho-cho, Mizuhoku, Nagoya, 467-8601, Japan

    Jiachi Ma, Hirozumi Sawai, Nobuo Ochi, Yoichi Matsuo, Donghui Xu, Akira Yasuda, Hiroki Takahashi, Takehiro Wakasugi & Hiromitsu Takeyama

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  1. Jiachi Ma
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  2. Hirozumi Sawai
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  3. Nobuo Ochi
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Correspondence to Hirozumi Sawai.

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Ma, J., Sawai, H., Ochi, N. et al. PTEN regulate angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells. Mol Cell Biochem 331, 161–171 (2009). https://doi.org/10.1007/s11010-009-0154-x

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  • DOI: https://doi.org/10.1007/s11010-009-0154-x

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