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Copyright © 2019 Lukas Perkhofer et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0/

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is still the Achilles heel in modern oncology, with an increasing incidence accompanied by a persisting high mortality. The developmental process of PDAC is thought to be stepwise via precursor lesions and sequential accumulation of mutations. Thereby, current sequencing studies recapitulate this genetic heterogeneity in PDAC and show besides a handful of driver mutations (KRAS, TP53) a plethora of passenger mutations that allow to define subtypes. However, modeling the mutations of interest and their effects is still challenging. Interestingly, organoids have the potential to recapitulate in vitro, the in vivo characteristics of the tissue they originate from. Here, we could establish and develop tools allowing us to isolate, culture, and genetically modify ductal mouse organoids. Transferred to known effectors in the IPMN-PDAC sequence, we could reveal significantly increased proliferative and self-renewal capacities for PTEN and RNF43 deficiency in the context of oncogenic KRASG12D in mouse pancreatic organoids. Overall, we were able to obtain promising data centering ductal organoids in the focus of future PDAC research.

Details

Title
Pancreatic Ductal Organoids React Kras Dependent to the Removal of Tumor Suppressive Roadblocks
Author
Perkhofer, Lukas; Engler, Melanie; Gout, Johann; Arnold, Frank; Morawe, Mareen; Breunig, Markus; Seufferlein, Thomas; Kleger, Alexander  VIAFID ORCID Logo  ; Pierre-Olivier Frappart  VIAFID ORCID Logo 
Editor
Holm Zaehres
Publication year
2019
Publication date
2019
Publisher
Hindawi Limited
ISSN
1687966X
e-ISSN
16879678
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2233710391
Copyright
Copyright © 2019 Lukas Perkhofer et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0/