Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression (original) (raw)
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Expression and functional significance of CDC25B in human pancreatic ductal adenocarcinoma
Oncogene, 2004
Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths. Deregulation of cell-cycle control is thought to be a crucial event in malignant transformation, and CDC25 phosphatases are a family of cyclin-dependent kinase activators, which act at different points of the cell cycle, including G1–S and G2–M transition. Here, we investigated the expression and functional significance of
PloS one, 2014
CDX2, a master transcriptional regulator of intestinal cell differentiation and survival, has been used as a marker to indicate colorectal lineage in adenocarcinomas of unknown origin. Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes for adenocarcinomas of unknown origin, but CDX2 expression in pancreatic disease remains unclear. In this study, we systemically and extensively investigated the expression and role of CDX2 in PDAC. We reported that CDX2 expression is weak and heterogeneous is all normal pancreas and chronic pancreatitis. It is largely expressed in epithelial-lining cells of pancreatic ducts including main ducts, inter-lobular ducts, intra-lobular ducts, intercalated ducts and centroacinar cells, but not in acinar cells or islet cells. CDX2 expression is down regulated during the transformation process from PanIN to PDAC. Only one third of PDACs retain some degree of CDX2 expression, and this group of PDACs have reduced median survival time compa...
Cancer, 2006
BACKGROUND. Cytokeratins are markers of epithelial cell differentiation useful in determining histogenesis for malignancies with an unknown primary. Application of this principle to a single malignancy may identify cancer subtypes with altered developmental programs. Herein, we investigate the relevance of two widely used cytokeratins (CKs), 7 and 20, to subtype pancreas cancer and identify associations with clinical features.
Pathology, 2010
Aims: Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis. Methods: We analysed the expression of p21, p27, p53 and Ki-67, in 210 ductal pancreatic adenocarcinomas, 40 PanlN-3 cases and 40 normal controls combined in a tissue microarray. The results were correlated with clinicopathological and follow-up data. Results: Our study revealed a differential p27, p21, p53, and Ki-67 expression between ductal adenocarcinoma, Pan1N-3 and normal pancreas. p27 expression progressively decreased from normal pancreas to PanlN and to pancreatic cancer. Decreased p27 and increased p53 expression showed a significant association with the T stage. A Ki-67 > 5% correlated with reduced survival. Conclusions: In pancreatic cancer, loss of p27 and increased p53 expression is associated with a more aggressive phenotype. p27 may play an important role in pancreatic carcinogenesis. A Ki-67 > 5% independently predicted poor outcome.
Kannan Subbaram, 2022
This short report describes the carcinogenesis of the pancreas leading to pancreatic ductal adenocarcinoma (PDAC) determined by molecular, cellular, and functional heterogeneity. Among the diverse types of pancreatic cancers, PDAC is the most lethal, aggressive, and one of the leading cancers associated with the highest mortality. Pancreatic cellular components like pancreatic stellate cells (PSC), mesenchymal stem cells (MSC), and pancreatic fibroblast cells (PFC) exhibit these properties in PDAC. After the appearance of point mutations in KRAS, the mutations in tumor suppressor genes appear sequentially in the order of CDKN2A, TP53, and SMAD4 that eventually resulting in PDAC development. As of today, there are no effective therapeutic options or treatments available for PDAC. The main difficulty in managing PDAC cases is its defiance to chemotherapy and radiotherapy. There were several attempts to identify a suitable biomarker for the early diagnosis and prognosis of PDAC. Anyway, these recently discovered biomarkers vary in their sensitivity and specificities. Some of the other important and reliable biomarkers for PDAC are carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cell migration-inducing hyaluronan binding protein (CE-MIP), serum fatty acid metabolite PC-594, and micro-RNAs (miRNAs).
2016
Pancreatic differentiation 2 (PD2), an important subunit of the human PAF complex, was identified after differential screening analysis of 19q13 amplicon, and its overexpression induces oncogenic transformation of NIH3T3 cells, hence raising the possibility of a role for PD2 in tumorigenesis and metastasis. To test this hypothesis, we analyzed here the functional role and clinical significance of PD2 in pancreatic ductal adenocarcinoma (PDAC) and its pathogenesis. Using immunohistochemical analysis, we found that PD2 is detected in the acini but not in the ducts in the normal pancreas. In human PDAC specimens, PD2 was instead primarily detected in the ducts (12/48 patients 25%; p-value < 0.0001), thereby showing that PDAC correlates with increased ductal expression of PD2. Consistently, PD2 expression was increased in telomerase-immortalized human pancreatic ductal cells (HPNE cells) modified to express the HPV16 E6 and E7 proteins, whose respective functions are to block p53 and...
Molecular biology of pancreatic cancer
Clinical and Translational Oncology, 2008
Pancreatic ductal adenocarcinoma is a dismal disease with a median survival of less than 6 months and an overall 5-year survival rate less than 1% . This bad prognosis is due to early lymphatic and hematogenic dissemination. Effective therapies for locally advanced or metastatic tumors are very limited and curatively resected patients experience relapse in over 80% of cases. Together, these findings reflect the aggressive biology of the disease. Here, we describe molecular mechanisms leading to unrestrained proliferation, insensitivity to growth inhibitory signals, evasion of apoptosis, limitless replicative potential, tissue invasion, metastasis and sustained angiogenesis. Potential therapeutic targets are highlighted.
PanINs and IPMNs are the two most common precursor lesions that can progress to invasive pancreatic ductal adenocarcinoma (PDA). DCLK1 has been identified as a biomarker of progenitor cells in PDA progressed from PanINs. To explore the potential role of DCLK1-expressing cells in the genesis of IPMNs, we compared the incidence of DCLK1-positive cells in pancreatic tissue samples from genetically-engineered mouse models (GEMMs) for IPMNs, PanINs, and acinar to ductal metaplasia by immuno-histochemistry and immunofluorescence. Mouse lineage tracing experiments in the IPMN GEMM showed that DCLK1 þ cells originated from a cell lineage distinct from PDX1 þ progenitors. The DCLK1 þ cells shared the features of tuft cells but were devoid of IPMN tumor biomarkers. The DCLK1 þ cells were detected in the earliest proliferative acinar clusters prior to the formation of metaplastic ductal cells, and were enriched in the " IPMN niches ". In summary, DCLK1 labels a unique pancreatic cellular lineage in the IPMN GEMM. The clustering of DCLK1 þ cells is an early event in Kras-induced pancreatic tumorigenesis and may contribute to IPMN initiation.