Abstract
The expression of hepatocyte growth factor (HGF) and c-Met is associated with tumor progression in many human malignancies. A recent study demonstrated HGF and c-Met expression in human salivary gland cancer tissues. Here, we investigated the role of the HGF/c-Met system in the invasive growth of two human salivary gland cancer cell lines: green fluorescent protein-adenoid cystic carcinoma 2 (GFP-ACC2) and GFP-ACCM. HGF enhanced the invasive growth of the two cell lines by activating PI3K/Akt signaling. All Akt isoforms (Akt1, Akt2, and Akt3) were detected in both cell types by Western blot analysis. Knockdown of any of the Akt isoforms using isoform-specific synthetic small-interfering RNAs largely abrogated the invasive growth induced by HGF. Our findings suggest that all of the Akt isoforms are required for the HGF-stimulated invasive growth of human salivary gland cancer cells, and that targeting a single Akt isoform could be effective in treating salivary gland cancers.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Carcinoma, Adenoid Cystic / enzymology*
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Carcinoma, Adenoid Cystic / pathology*
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Hepatocyte Growth Factor / metabolism
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Hepatocyte Growth Factor / pharmacology
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Humans
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Neoplasm Invasiveness
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Proto-Oncogene Proteins c-met / antagonists & inhibitors
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Proto-Oncogene Proteins c-met / genetics
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Proto-Oncogene Proteins c-met / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / pharmacology
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Salivary Gland Neoplasms / enzymology*
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Salivary Gland Neoplasms / pathology*
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Signal Transduction
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Tumor Cells, Cultured
Substances
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Isoenzymes
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Phosphoinositide-3 Kinase Inhibitors
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RNA, Small Interfering
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Hepatocyte Growth Factor
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Proto-Oncogene Proteins c-met
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Proto-Oncogene Proteins c-akt