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Title: Promoter-Level Transcriptome Identifies Stemness Associated With Relatively High Proliferation in Pancreatic Cancer Cells
Authors: Chen, Ru
Sugiyama, Aiko
Kataoka, Naoyuki
Sugimoto, Masahiro
Yokoyama, Shoko
Fukuda, Akihisa  kyouindb  KAKEN_id
Takaishi, Shigeo  kyouindb  KAKEN_id  orcid (unconfirmed)
Seno, Hiroshi
Author's alias: 陳, 茹
杉山, 愛子
片岡, 直行
杉本, 昌弘
横山, 尚子
福田, 晃久
高石, 繁生
妹尾, 浩
Keywords: cap analysis of gene expression
intraductal papillary mucinous neoplasm
molecular profiling
pancreatic intraepithelial neoplasia
Issue Date: 20-Mar-2020
Publisher: Frontiers Media SA
Journal title: Frontiers in Oncology
Volume: 10
Thesis number: 316
Abstract: Both pancreatic intraepithelial neoplasia (PanIN), a frequent precursor of pancreatic cancer, and intraductal papillary mucinous neoplasm (IPMN), a less common precursor, undergo several phases of molecular conversions and finally develop into highly malignant solid tumors with negative effects on the quality of life. We approached this long-standing issue by examining the following PanIN/IPMN cell lines derived from mouse models of pancreatic cancer: Ptf1a-Cre; KrasG12D; p53f/+ and Ptf1a-Cre; KrasG12D; and Brg1f/f pancreatic ductal adenocarcinomas (PDAs). The mRNA from these cells was subjected to a cap analysis of gene expression (CAGE) to map the transcription starting sites and quantify the expression of promoters across the genome. Two RNA samples extracted from three individual subcutaneous tumors generated by the transplantation of PanIN or IPMN cancer cell lines were used to generate libraries and Illumina Seq, with four RNA samples in total, to depict discrete transcriptional network between IPMN and PanIN. Moreover, in IPMN cells, the transcriptome tended to be enriched for suppressive and inhibitory biological processes. In contrast, the transcriptome of PanIN cells exhibited properties of stemness. Notably, the proliferation capacity of the latter cells in culture was only minimally constrained by well-known chemotherapy drugs such as GSK690693 and gemcitabine. The various transcriptional factor network systems detected in PanIN and IPMN cells reflect the distinct molecular profiles of these cell types. Further, we hope that these findings will enhance our mechanistic understanding of the characteristic molecular alterations underlying pancreatic cancer precursors. These data may provide a promising direction for therapeutic research.
Rights: © 2020 Chen, Sugiyama, Kataoka, Sugimoto, Yokoyama, Fukuda, Takaishi and Seno. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
DOI(Published Version): 10.3389/fonc.2020.00316
PubMed ID: 32266133
Appears in Collections:Journal Articles

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