title: Alpha-fetoprotein: a new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines.
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.
authors.affiliation: Key Laboratory of Molecular Biology, Hainan Medical College, Haikou, Hainan, China.
authors.forename: Mengsen
authors.initials: M
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Chaoying
authors.initials: C
authors.lastname: Li
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Liu
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhou
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.forename: Michael A
authors.initials: MA
authors.lastname: McNutt
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000172:deficiency; D002879:Chromosomes, Human, Pair 10; D031541:Fluorescence Resonance Energy Transfer; D017353:Gene Deletion; D006706:Homeostasis; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008840:Microfilament Proteins / Q000172:deficiency; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D000070876:Tensins; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000235:genetics / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D000070876:Tensins; D025521:Tumor Suppressor Proteins; D000509:alpha-Fetoproteins; D014212:Tretinoin; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human