51 research outputs found
334 Construction of a PRO-Survival Wnt-Secreting Niche by Intestinal Cancer Cells Requires Cell Division Cycle 42
129 Cell Division Cycle 42 Is Essential for Intestinal Crypt Homeostasis and Brush Border Morphogenesis
Plasmalemma Vesicle Associated Protein Truncation Causes Lethal Protein-Losing Enteropathy in Humans
396 Colorectal Cancer Cells Exploit the Pleiotropic Functions of Cell Division Cycle 42 for Immediate PRO-Survival Niche Construction
Increased Bcl-xL Expression in Pancreatic Neoplasia Promotes Carcinogenesis by Inhibiting Senescence and ApoptosisSummary
Background & Aims: Bcl-xL, an anti-apoptotic Bcl-2 family protein, is overexpressed in 90% of pancreatic ductal adenocarcinoma (PDAC) cases. However, Bcl-xL expression in pancreatic intraepithelial neoplasias (PanINs) and its significance in PDAC carcinogenesis remain unclear. The aim of this study was to elucidate the significance of Bcl-xL expression in PanINs. Methods: We investigated the expression levels of Bcl-xL in pancreas-specific KrasG12D (P-KrasG12D) mice and human PanINs and PDAC. We examined the impact of Bcl-xL expression on Kras-mutated pancreatic neoplasia using Bcl-xLâoverexpressing P-KrasG12D mice and Bcl-xLâknockout P-KrasG12D mice. Results: In P-KrasG12D mice, the number of PanINs increased and their grades progressed with age. In total, 55.6% of these mice developed PDAC at 12â14 months. According to the immunohistochemistry of mouse pancreas and human resected specimens, Bcl-xL expression was increased significantly in PanIN-1 compared with that in normal pancreatic ducts, and augmented further with the progression of pancreatic neoplasia in PanIN-2/3 and PDAC. Oncogene-induced senescence was observed frequently in PanIN-1, but rarely was detected in PanIN-2/3 and PDAC. Bcl-xL overexpression significantly accelerated the progression to high-grade PanINs and PDAC and reduced the survival of P-KrasG12D mice. Bcl-xL overexpression in P-KrasG12D mice suppressed oncogene-induced senescence in PanIN-1 and inhibited apoptosis in PanIN-3. Bcl-xL deficiency in P-KrasG12D mice induced cellular senescence in PanIN-2/3. Conclusions: Bcl-xL expression increases with the progression from PanIN-1 to PDAC, whereas oncogene-induced senescence decreases. Bcl-xL overexpression increases PDAC incidence rates by inhibiting oncogene-induced senescence and apoptosis in PanINs. Conversely, Bcl-xL deficiency induced senescence in PanINs. AntiâBcl-xL treatments may have the potency to suppress the progression from PanINs to PDAC. Keywords: Kras, PanINs, Bcl-2 Family Protei
257 Basal Autophagy Plays an Important Role in Maintaining the Integrity of Pancreatic Acinar Cells in Mice
A case report of hepatocellular carcinoma adjacent to hepatic biloma successfully treated by stereotactic body radiation therapy
794e Lack of Basal Autophagy in Pancreatic Acinar Cells Develops Chronic Pancreatitis in Mice
364 The Significance of BCL-XL in the Development of KrasG12D-Driven Pancreatic Neoplasia
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