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A novel in vitro pancreatic carcinogenesis model

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Author(s)
Hyo Jin KangYoung Bin HongHee Jeong KimYong Weon YiRaghu G. NathYoung Soo ChangHo-Chan ChoInsoo Bae
Keimyung Author(s)
Cho, Ho Chan
Department
Dept. of Internal Medicine (내과학)
Journal Title
Toxicology Letters
Issued Date
2011
Volume
202
Issue
1
Keyword
AhRCYP1A1Pancreatic cancerBenzo(a)pyreneTCDDBRCA1
Abstract
Environmental factors (e.g., BaP) have been pointed out as one of the etiologies of pancreatic cancer.
However, very limited experimental assays are available to identify pancreatic specific environmen-
tal mutagens or susceptibility genes. In this study, we have developed a simple in vitro cell culture
model system that can be used to study the molecular and biochemical aspects of carcinogenesis in
a near-normal immortalized pancreatic ductal epithelial cell lines. In order to demonstrate that xeno-
biotic stress response is intact in these cells, we employed standard molecular biology techniques. For
examples, luciferase reporter and/or real-time quantitative PCR assays were used to determine stress-
induced CYP1A1 and CYP1B1 gene expression.Western blotting and immunocytochemistry assays were
used to demonstrate that TCDD or BaP could activate AhR signaling. For exploring the carcinogenesis
mechanism, we incubated cells with [3H]BaP and determined BaP–DNA binding activity by measuring
its radioactivity. BaP–DNA adduct formation was further confirmed by [32P]-postlabeling assay. Finally,
we demonstrated the effects of endogenous AhR or BRCA1 in BaP–DNA adduct accumulation in our cell
system. As results, no apparent BaP–DNA adduct accumulation by [32P]-postlabeling assay was found in
either control-siRNA or AhR-siRNA pretreated cells. On the other hand, a significant increase of BaP–DNA
adduct accumulation was found in BRCA1 knockdown cells. In conclusion, we suggest that this in vitro
model may provide the feasibility for future studies on the molecular basis of pancreatic ductal cell
carcinogenesis caused by dietary mutagens.
© 2011 Elsevier Ireland Ltd. All rights reserved. Keywords:
AhR
CYP1A1
Pancreatic cancer
Benzo(a)pyrene
TCDD
BRCA1
Keimyung Author(s)(Kor)
조호찬
Publisher
School of Medicine
Citation
Hyo Jin Kang et al. (2011). A novel in vitro pancreatic carcinogenesis model. Toxicology Letters, 202(1), 15–22. doi: 10.1016/j.toxlet.2011.01.012
Type
Article
ISSN
0378-4274
DOI
10.1016/j.toxlet.2011.01.012
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34674
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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