|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0002210,
umls-concept:C0007600,
umls-concept:C0037083,
umls-concept:C0044602,
umls-concept:C0086418,
umls-concept:C0164786,
umls-concept:C0178719,
umls-concept:C0285761,
umls-concept:C0567416,
umls-concept:C0677626,
umls-concept:C0680022,
umls-concept:C0812228,
umls-concept:C0851285,
umls-concept:C1150481,
umls-concept:C1368105,
umls-concept:C1451005,
umls-concept:C1705325,
umls-concept:C1710082
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2010-11-29
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|
pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Feb
|
|
pubmed:issn |
1097-0215
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|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
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pubmed:volume |
128
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
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pubmed:pagination |
524-32
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|
pubmed:meshHeading |
pubmed-meshheading:20473866-Carcinoma, Hepatocellular,
pubmed-meshheading:20473866-Cell Adhesion Molecules,
pubmed-meshheading:20473866-Chromosomes, Human, Pair 10,
pubmed-meshheading:20473866-Fluorescence Resonance Energy Transfer,
pubmed-meshheading:20473866-Gene Deletion,
pubmed-meshheading:20473866-Homeostasis,
pubmed-meshheading:20473866-Humans,
pubmed-meshheading:20473866-Liver Neoplasms,
pubmed-meshheading:20473866-Microfilament Proteins,
pubmed-meshheading:20473866-PTEN Phosphohydrolase,
pubmed-meshheading:20473866-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20473866-RNA Interference,
pubmed-meshheading:20473866-Signal Transduction,
pubmed-meshheading:20473866-Transfection,
pubmed-meshheading:20473866-Tretinoin,
pubmed-meshheading:20473866-Tumor Suppressor Proteins,
pubmed-meshheading:20473866-Up-Regulation,
pubmed-meshheading:20473866-alpha-Fetoproteins
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|
pubmed:year |
2011
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|
pubmed:articleTitle |
Alpha-fetoprotein: a new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines.
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|
pubmed:affiliation |
Key Laboratory of Molecular Biology, Hainan Medical College, Haikou, Hainan, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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