Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 μmol/L). Real-time fluorescent quantitative PCR (qRT-PCR) was performed to detect the level of HIF-1α mRNA, and Western blotting to detect the HIF-1α protein level, the phosphorylation levels of ERK1/2 and AKT. Results SCF and HIF-1α were up-regulated in pancreatic cancer samples and they had an obvious positive correlation. In PANC-1 cells, SCF didn't affect the expression of HIF-1α mRNA, but up-regulated the expression of HIF-1α protein in a dose-dependent manner. Gleevec inhibited the SCF-induced up-regulation of HIF-1α protein, but did not affect the mRNA. And Gleevec blocked the phosphorylation of AKT and ERK1/2. Conclusion SCF/c-KIT can up-regulate the protein expression of HIF-1α by activating AKT and ERK signaling pathways in pancreatic cancer cells.
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Cell Rep
January 2025
Ministry of Education Key Laboratory of Biosystems Homeostasis & Protection, College of Life Sciences, Zhejiang University, Hangzhou, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang Provincial Key Laboratory of Pancreatic Disease, School of Medicine, Zhejiang University, Hangzhou, China; Cancer Center, Zhejiang University, Hangzhou, China. Electronic address:
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Urology Department, Dorset County Hospital, Dorchester, UK.
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Department of Integrative Physiology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
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Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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View Article and Find Full Text PDFOncogene
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Department of Gastroenterology, Endocrinology and Metabolism, Center for Tumor and Immune Biology, Philipps University Marburg, Marburg, Germany.
The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.
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