From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with K-ras status analysis

Fernandez, Carla; Chetaille, Bruno; Taséi, Anne-Marie; Sastre, B.; Sahel, J; Payan-Defais, Marie-José

doi:10.1016/s0399-8320(05)80818-8

Cited by 8 publications

(3 citation statements)

References 12 publications

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“…Increasing evidence has demonstrated that PanIN is the most direct precursor lesion of PDAC [ 34 ]. Studies have shown that patients with benign pancreatic tumors whose surgery margin had high-grade PanIN were diagnosed with PDAC several months or several years after the surgery [ 35 – 37 ]. The molecular alteration is accumulated during the progression from PanIN to PDAC [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…The molecular alteration is accumulated during the progression from PanIN to PDAC [ 38 ]. Kirsten ras oncogene ( KRAS ) mutation was found in 36% of PanIN1A cases, 44% of PanIN1B cases, 87% of PanIN2/3 cases, and more than 90% of PDACs [ 35 , 39 ]; therefore, KRAS mutation was considered an early genetic alteration event of PDAC [ 40 ]. Cyclin-dependent kinase inhibitor 2A ( CDKN2A ) mutation can be found in PanIN2, and mutations of tumor protein p53 ( TP53 ), breast cancer 2 ( BRCA2 ), and SMAD family member 4 ( SMAD4 ) were found mainly in PanIN3 or PDAC, which were recognized as late events of PDAC initiation [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

et al. 2016

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BackgroundMicroRNA-506 (miR-506) has been reported to function in several tumors as a tumor suppressor gene or oncogene. However, the expression and role of miR-506 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we aimed to evaluate the phenotype of miR-506 in PDAC.MethodsUsing miRNA in situ hybridization, we examined the expression of miR-506 in 113 PDACs and 87 paired normal pancreatic tissues. We evaluated miR-506 expression in PDAC cells, normal pancreatic ducts, and acinus/islands, and we analyzed the associations between miR-506 expression and the clinicopathologic characteristics of PDAC patients.ResultsmiR-506 expression was higher in PDAC than in matched normal pancreatic ductal cells (P < 0.001). On the other hand, the combined group of well and moderately differentiated PDACs showed higher levels of miR-506 than the poorly differentiated ones (P = 0.023). Moreover, miR-506 expression was negatively associated with pathologic T category (P = 0.004) and lymph node metastasis (P = 0.033), suggesting that miR-506 might inhibit the progression of PDAC.ConclusionsOur results suggest that miR-506 either plays a role as an oncogene in the tumorigenesis and a tumor suppressor in the progression or serves as a house-keeping, tumor-suppressing miRNA, whose expression can be activated by oncogenic signals in early development to hinder the progression of PDAC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

et al. 2016

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“…Activating point mutations in the KRAS gene are present in ~95% of pancreatic cancers 40–42 and represent the earliest molecular events involved in pancreatic carcinogenesis 43,44 . Membrane-bound KRAS protein is another crucial biomarker of protein prenylation which is required for anchoring of proteins to the cytosolic membrane and for their activity 13,14 .…”

Section: Discussionmentioning

confidence: 99%

Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma

et al. 2012

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Aldo-keto reductase family 1B10 (AKR1B10) exhibits more restricted lipid substrate specificity (including farnesal, geranylgeranial, retinal and carbonyls), a n d metabolizing these lipid substrates plays a crucial role in promoting carcinogenesis. Overexpression of AKR1B10 has been identified in smoking-related carcinomas such as lung cancer. As development of pancreatic cancer is firmly linked to smoking, the aim of the present study was to examine the expression and oncogenic role of AKR1B10 in pancreatic adenocarcinoma. AKR1B10 expression was analyzed in 50 paraffin-embedded clinical pancreatic cancer samples using immunohistochemistry. Oncogenic function of AKR1B10 was examined in pancreatic carcinoma cells in vitro using western blotting and siRNA approaches, mainly on cell apoptosis and protein prenylation including KRAS protein and its downstream signals. Immunohistochemistry analysis revealed that AKR1B10 over-expressed in 70% (35/50) of pancreatic adenocarcinomas and majority of pancreatic intraepithelial neoplasia, but not in adjacent morphologically normal pancreatic tissue. Compared to a normal pancreatic ductal epithelial cell (HPDE6E7), all of six cultured pancreatic adenocarcinoma cell lines had a over-expression of AKR1B10 using immunoblotting, which correlated with increase of enzyme activity. siRNA-mediated silencing of AKR1B10 expression in pancreatic cancer cells resulted in 1) increased cell apoptosis, 2) increased non-farnesyled HDJ2 protein, and 3) decreased membrane-bound prenylated KRAS protein and its downstream signaling molecules including phosphorylated ERK and MEK and membrane-bound E-cadherin. Our findings provide first time evidence of that AKR1B10 is a unique enzyme involved in pancreatic carcinogenesis possibly via modulation of cell apoptosis and protein prenylation.

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Inhibition of Pancreatitis and Carcinogenesis by Capsaicin

Zhang

Liao

et al. 2013

Role of Capsaicin in Oxidative Stress and Cancer

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From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with K-ras status analysis

Cited by 8 publications

References 12 publications

MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression

Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma

Inhibition of Pancreatitis and Carcinogenesis by Capsaicin

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