کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3317736 | 1211570 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Loss of Heterozygosity Status of D9S105 Marker Is Associated with Downregulation of Krüppel-Like Factor 4 Expression in Pancreatic Ductal Adenocarcinoma and Pancreatic Intraepithelial Lesions
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The transcription factor Krüppel-like factor 4 (KLF4) may act both as an oncogene and a tumor suppressor in a tissue-dependent manner, and further studies on its role in pancreatic ductal adenocarcinoma (PDAC) progression and clinical outcome are warranted. Therefore, we investigated the loss of heterozygosity (LOH) in the 9q22.3-32 region and loss of KFL4 gene expression in epithelial cells from 35 PDAC, 6 pancreatic intraductal neoplasias (PanINs) and 6 normal ducts, isolated by laser microdissection, as well as their correlation with overall survival (OS) in patients treated with gemcitabine in the adjuvant setting. LOH was evaluated with 4 microsatellite markers and in situ hybridization, while KLF4 expression was studied by reverse transcription-PCR and immunohistochemistry. LOH in at least 1 locus was observed in 25 of 35 PDAC cases and in 5 of 6 PanINs, respectively. In particular, the loss of the D9S105 marker was present in 46.9% of PDAC and 83.3% of PanlNs, becoming the most deleted marker, while no LOH in D9S105 was observed in normal Wir-sung pancreatic duct. Lack of KLF4 mRNA expression was significantly associated with: (1) genomic deletion flanking KLF4 in PDAC and in PanINs (with LOH of D9S105), (2) low-grade PDAC-associated PanIN, (3) lack of KLF4 protein expression, and (4) shorter OS. These results strongly suggest a relationship between D9S105 deletion and downregulation of KLF4 gene expression as an early event in PDAC progression, as well as a possible role of KLF4 as a prognostic biomarker in gemcitabine-treated patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pancreatology - Volume 11, Issue 1, June 2011, Pages 30-42
Journal: Pancreatology - Volume 11, Issue 1, June 2011, Pages 30-42
نویسندگان
Niccola Funel, Mariangela Morelli, Elisa Giovannetti, Marco Del Chiaro, Luca Emanuele Pollina, Franco Mosca, Ugo Boggi, Andrea Cavazzana, Daniela Campani,