Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma.

Proceedings of the National Academy of Sciences of the United States of America
Pawel K MazurJens T Siveke

Abstract

Pancreatic cancer is one of the most fatal malignancies lacking effective therapies. Notch signaling is a key regulator of cell fate specification and pancreatic cancer development; however, the role of individual Notch receptors and downstream signaling is largely unknown. Here, we show that Notch2 is predominantly expressed in ductal cells and pancreatic intraepithelial neoplasia (PanIN) lesions. Using genetically engineered mice, we demonstrate the effect of conditional Notch receptor ablation in KrasG12D-driven pancreatic carcinogenesis. Deficiency of Notch2 but not Notch1 stops PanIN progression, prolongs survival, and leads to a phenotypical switch toward anaplastic pancreatic cancer with epithelial-mesenchymal transition. By expression profiling, we identified increased Myc signaling regulated by Notch2 during tumor development, placing Notch2 as a central regulator of PanIN progression and malignant transformation. Our study supports the concept of distinctive roles of individual Notch receptors in cancer development.

References

Apr 16, 2002·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·C SchlegerU Bleyl
Oct 2, 2003·Nature·Sarah P ThayerMatthias Hebrok
Jan 1, 2004·Genes & Development·Luika A TimmermanJosé Luis de la Pompa
Jan 7, 2004·Cancer Cell·Sunil R HingoraniDavid A Tuveson
Jun 1, 2005·Laboratory Investigation; a Journal of Technical Methods and Pathology·Kwang M LeeMichel M Ouellette
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Nabeel BardeesyRonald A Depinho
May 17, 2006·Genes & Development·Aram F HezelRonald A Depinho
Jun 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Apostolos KlinakisArgiris Efstratiadis
Sep 7, 2006·Molecular and Cellular Biology·Vishva Mitra SharmaMichelle A Kelliher
Sep 28, 2006·The American Journal of Pathology·Ilse RoomanLuc Bouwens
Nov 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Teresa PalomeroAdolfo A Ferrando
Nov 23, 2006·Genes & Development·Marina Pasca di MaglianoMatthias Hebrok
Jan 31, 2007·The Journal of Experimental Medicine·Valerie BesseyriasFreddy Radtke
Jun 27, 2007·The American Journal of Pathology·Liqin ZhuStephen F Konieczny
Nov 6, 2007·PloS One·Marina Pasca di MaglianoMatthias Hebrok
Feb 5, 2008·Gastroenterology·Jens T SivekeRoland M Schmid
Apr 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cecilia SahlgrenUrban Lendahl
Jul 19, 2008·Development·Hassan NakhaiRoland M Schmid
Aug 22, 2008·Development·Hassan NakhaiRoland M Schmid
Nov 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nils HabbeAnirban Maitra
Nov 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jean-Paul De La OL Charles Murtaugh
Apr 18, 2009·Electrophoresis·Sheng PanTeresa A Brentnall
Jun 9, 2009·Gastroenterology·Baoan JiCraig D Logsdon
Jul 16, 2009·Molecular Carcinogenesis·Carolin SchildGünter Schneider
Oct 28, 2009·Proceedings of the National Academy of Sciences of the United States of America·Manran LiuRichard G Pestell
Dec 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Meritxell RoviraSteven D Leach
Jan 15, 2010·The Journal of Clinical Investigation·John P MorrisMatthias Hebrok

❮ Previous
Next ❯

Citations

Mar 21, 2012·Langenbeck's Archives of Surgery·Ivonne RegelJörg Kleeff
Nov 2, 2012·Cancer Metastasis Reviews·Wanglong Qiu, Gloria H Su
Mar 20, 2013·Molecular Oncology·Carmen Guerra, Mariano Barbacid
Apr 22, 2011·Nature Reviews. Cancer·Prathibha RanganathanAnthony J Capobianco
Aug 31, 2011·The Journal of Experimental Medicine·Patrick ViatourJulien Sage
Sep 29, 2011·The Journal of Experimental Medicine·Camille LobryIannis Aifantis
Feb 22, 2012·The Journal of Experimental Medicine·Natalie CookDavid A Tuveson
Aug 15, 2012·The Journal of Experimental Medicine·Mark J KielKojo S J Elenitoba-Johnson
Nov 29, 2012·The Cancer Journal·Pelin Cinar, Margaret A Tempero
Nov 29, 2012·The Cancer Journal·Christoph Benedikt Westphalen, Kenneth P Olive
Jan 8, 2014·Genes & Development·Michael SaborowskiScott W Lowe
Dec 29, 2010·Journal of Oncology·Fatima RangwalaAnna Mae Diehl
Dec 12, 2013·Molecular Cancer·Ming QuanKeping Xie
Jun 12, 2013·Annals of Surgical Oncology·Ioannis T KonstantinidisPeter J Allen
Dec 12, 2012·PloS One·Christopher D MannMargaret M Manson
Jun 10, 2014·The Journal of Clinical Investigation·Chi-Hong ChaoChun-Ju Chang
Mar 4, 2014·Carcinogenesis·Jennifer M BaileyHoward C Crawford
Oct 13, 2014·Journal of the National Cancer Institute·Dimitris StellasArgiris Efstratiadis
Nov 25, 2014·BMC Cancer·Marsha M ThomasMarina Pasca di Magliano
Aug 23, 2011·Journal of Gastroenterology·Dyah Laksmi DewiMasaki Mori
Feb 13, 2016·Acta histochemica·A GharibiJ A Kelber
Mar 22, 2016·Cellular and Molecular Gastroenterology and Hepatology·Huiyuan TangBrian B Haab
Mar 13, 2012·Gastroenterology·Pedro A Pérez-ManceraDavid A Tuveson
Jun 21, 2011·Gastroenterology·Irina HeidJens T Siveke
Jun 17, 2016·Molecular & Cellular Oncology·Geou-Yarh LiouMichael Leitges
Dec 14, 2011·Molecular Carcinogenesis·Angela L McCleary-WheelerMartin E Fernandez-Zapico
Sep 15, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Irene EspositoGünter Klöppel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Ductal

Ductal carcinoma is a malignant neoplasm involving the ductal systems of any of a number of organs, such as the mammary glands, pancreas, prostate or lacrimal gland. Discover the latest research on ductal carcinoma here.

Cell Fate Specification

Cell fate specification is determined by complex signal transduction pathways including Notch and the Sonic hedgehog signaling pathway. Here is the latest research on regulation of cell fate determination.

© 2021 Meta ULC. All rights reserved