Downregulation of STAT3 signaling induces apoptosis but also promotes anti-apoptotic gene expression in human pancreatic cancer cell lines
| Autor: | Eva Hausmann, Lothar Bergmann, Wolfgang Glienke |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
Cell Survival Survivin bcl-X Protein Down-Regulation Apoptosis Biology medicine.disease_cause Inhibitor of Apoptosis Proteins Downregulation and upregulation Cell Line Tumor Pancreatic cancer medicine Humans STAT3 Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction General Medicine medicine.disease Cell biology Gene Expression Regulation Neoplastic Pancreatic Neoplasms biology.protein Cancer research Signal transduction Carcinogenesis |
| Zdroj: | Tumor Biology. 32:493-500 |
| ISSN: | 1423-0380 1010-4283 |
| DOI: | 10.1007/s13277-010-0143-4 |
| Popis: | Signal transducer and activator of transcription 3 (STAT3) is a key regulator of cytokine signaling pathways that regulates gene expression. In pancreatic cancer, constitutive activation of STAT3 contributes to oncogenesis by preventing apoptosis through upregulation of anti-apoptotic proteins. We have examined the inhibition of STAT3 as a potential therapeutic approach in pancreatic cancer. siRNA targeting STAT3 was used to evaluate the role of STAT3 in modulating the expression of Survivin/BIRC5 and BCL-xL in the pancreatic cancer cell lines PANC-1 and BxPC-3 and induction of apoptosis. Expression of STAT3, Survivin/BIRC5, and BCL-xL on mRNA and protein level was measured by real-time RT-PCR and Western blot analysis 24, 48, and 72 h after transfection. STAT3 downregulation resulted in a decrease of cell viability in both cell lines and induced apoptosis in BxPC-3 cells. Despite significant inhibition of STAT3, the expression of the anti-apoptotic genes Survivin/BIRC5 and BCL-xL were not subsequently downregulated. Even more, the cell line BxPC-3 shows a significant increase of Survivin/BIRC5 and BCL-xL mRNA after 48-72 h as a result of STAT3 downregulation. Inactivation of STAT3 in pancreatic cancer cell lines induces apoptosis but also may promote the expression of anti-apoptotic genes. |
| Databáze: | OpenAIRE |
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