Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-03-08

AUTHORS

Jonghyeob Lee, Emily R Snyder, Yinghua Liu, Xueying Gu, Jing Wang, Brittany M Flowers, Yoo Jung Kim, Sangbin Park, Gregory L Szot, Ralph H Hruban, Teri A Longacre, Seung K Kim

ABSTRACT

Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. More... »

PAGES

14686

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms14686

DOI

http://dx.doi.org/10.1038/ncomms14686

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084128914

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28272465


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/ncomms14686'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/ncomms14686'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/ncomms14686'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/ncomms14686'


 

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