Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors
| Autor: | Thankam S. Nair, Thomas E. Carey, Yo Ueda, T Tono, Kiyoshi Misawa, Pavan K. Kommareddi, Yuki Misawa, Takeharu Kanazawa, Toshihide Iwashita |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Fas Ligand Protein Immunoblotting Galanin receptor Galanin Biology Transfection Colony-Forming Units Assay Phosphatidylinositol 3-Kinases Cyclin D1 Genetics Tumor Cells Cultured Humans Molecular Biology PI3K/AKT/mTOR pathway Cell Proliferation Cyclin-Dependent Kinase Inhibitor Proteins Oligonucleotide Array Sequence Analysis Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Reverse Transcriptase Polymerase Chain Reaction Receptor Galanin Type 1 Squamous carcinoma Enzyme Activation Cancer research Carcinoma Squamous Cell Mouth Neoplasms Signal transduction Cyclin-dependent kinase inhibitor protein Galanin receptor 1 Signal Transduction |
| Zdroj: | Oncogene. 26(39) |
| ISSN: | 0950-9232 |
| Popis: | Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27(Kip1) and p57(Kip2). Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Galphai, not the PI3K pathway-linked to the Gbetagamma subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation. |
| Databáze: | OpenAIRE |
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