Role of Akt isoforms in HGF-induced invasive growth of human salivary gland cancer cells.

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.

• Authors: Shingo Hara, Koh-Ichi Nakashiro, Hiroyuki Goda, Hiroyuki Hamakawa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 370 Issue 1 Pg. 123-8 (May 23 2008) ISSN: 1090-2104 [Electronic] United States
• PMID: 18355439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Isoenzymes
• Phosphoinositide-3 Kinase Inhibitors
• RNA, Small Interfering
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met
• Proto-Oncogene Proteins c-akt

Topics

• Base Sequence
• Carcinoma, Adenoid Cystic (enzymology, pathology)
• Hepatocyte Growth Factor (metabolism, pharmacology)
• Humans
• Isoenzymes (antagonists & inhibitors, genetics, metabolism)
• Neoplasm Invasiveness
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-met (antagonists & inhibitors, genetics, metabolism)
• RNA, Small Interfering (genetics, pharmacology)
• Salivary Gland Neoplasms (enzymology, pathology)
• Signal Transduction
• Tumor Cells, Cultured