Role of phosphatidylinositol-3 kinase/Akt pathway in bladder cancer cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand
| Autor: | Natsuo Oka, Ryuichi Taue, Hirofumi Izaki, Hiro-omi Kanayama, Tomoteru Kishimoto, Shuji Tanimoto, Masaaki Nishitani, Tomoharu Fukumori, Hiroyoshi Nakatsuji, Masayuki Takahashi |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
medicine.medical_specialty Programmed cell death Cell Survival Apoptosis TNF-Related Apoptosis-Inducing Ligand Wortmannin Phosphatidylinositol 3-Kinases chemistry.chemical_compound Cell Line Tumor Internal medicine medicine Humans Protein kinase B PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Membrane Glycoproteins Caspase 3 Tumor Necrosis Factor-alpha business.industry Akt/PKB signaling pathway General Medicine Caspase 9 Endocrinology Urinary Bladder Neoplasms Oncology chemistry Drug Resistance Neoplasm Caspases Cancer cell Cancer research Tumor necrosis factor alpha Apoptosis Regulatory Proteins business Proto-Oncogene Proteins c-akt |
| Zdroj: | Cancer Science. 97:1093-1098 |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | TRAIL/Apo2L is a pro-apoptotic cytokine that is capable of inducing apoptosis in a wide variety of cancer cells but not in normal cells. Among various molecular strategies by which cancer cells evade apoptosis, PI3K/Akt signaling represents a dominant survival pathway. In this report, we investigated the role of PI3K/Akt pathway in TRAIL-induced apoptotic death in human bladder cancer cells. We observed that RT4 cells had very low level of constitutively active Akt and were sensitive to TRAIL, whereas UM-UC-3 and T24 cells had higher levels of constitutively active Akt and were resistant to TRAIL. Downregulation of constitutively active Akt by PI3K inhibitors, wortmannin and LY294002, reversed cellular resistance to TRAIL. However, transfecting constitutively active Akt into RT4 cells increased Akt activity and inhibited TRAIL-induced apoptosis. These results suggest that elevated Akt activity protects UM-UC-3 and T24 cells from TRAIL-induced apoptosis, and the PI3K/Akt signaling might inhibit apoptotic signals. Thus, the modulation of Akt activity by combining pharmacological drugs or genetic alterations of the Akt expression could induce cellular responsiveness to TRAIL and PI3K/Akt signaling pathway could serve as a novel target for therapeutic intervention in bladder cancer. |
| Databáze: | OpenAIRE |
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