title: Downregulation of STAT3 signaling induces apoptosis but also promotes anti-apoptotic gene expression in human pancreatic cancer cell lines.
abstract: 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.
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, University Hospital, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Glienke
authors.forename: Eva
authors.initials: E
authors.lastname: Hausmann
authors.forename: Lothar
authors.initials: L
authors.lastname: Bergmann
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000077022:Survivin; D051020:bcl-X Protein / Q000032:analysis / Q000235:genetics
chemical_list: C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D051020:bcl-X Protein