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Alpha-fetoprotein: A new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines

✍ Scribed by Mengsen Li; Hui Li; Chaoying Li; Shanshan Wang; Wei Jiang; Zhongmin Liu; Sheng Zhou; Xinhua Liu; Michael A. McNutt; Gang Li

Publisher
John Wiley and Sons
Year
2010
Tongue
French
Weight
595 KB
Volume
128
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

Despite its well‐defined role as a serum growth factor during fetal liver development and hepatic oncogenesis, the biological significance of cytoplasmic alpha‐fetoprotein (AFP) remains incompletely understood. Here, we provide evidence to illustrate that cytoplasmic AFP may function as a regulator in the phosphatidylinositol 3‐kinase (PI3K)/AKT pathway in human hepatocellular carcinoma cells. The results demonstrated colocalization and interaction of AFP and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in the cytoplasm of AFP‐producing Bel 7402 and HepG2 cells, with an interaction distance of 12.6 ± 2.7 Å as determined with the fluorescence resonance energy transfer technique. Knockdown of AFP mRNA or inhibition of AFP expression by all trans‐retinoic acid resulted in enhancement of the PTEN level with a synchronous decrease in phosphorylated AKT. Transfection of the afp gene into HLE cells (originally AFP negative) led to a significant activation of AKT signaling. The inhibition of PI3K signaling by LY 294002 was simultaneously reversed by transfection, accompanied by diminution of all trans‐retinoic acid‐induced upregulation of PTEN and enhancement of cell growth. In conclusion, these results demonstrate that cytoplasmic AFP is involved in regulation of hepatocellular growth and tumorigenesis.

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