Krebsforum Lazarus

Bitte loggen sie sich ein oder registrieren sie sich.

Einloggen mit Benutzername, Passwort und Sitzungslänge
Erweiterte Suche  

Autor Thema: Study about origins of one type of deadly pancreatic cancer.  (Gelesen 966 mal)


  • Globaler Moderator
  • Held Mitglied
  • *****
  • Beiträge: 848

UC San Francisco ‏@UCSF

STUDY: Scientists shed light on the origins of one type of deadly pancreatic cancer.

The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma

Guido von Figura, Akihisa Fukuda, Nilotpal Roy, Muluye E. Liku, John P. Morris IV, Grace E. Kim, Holger A. Russ, Matthew A. Firpo, Sean J. Mulvihill, David W. Dawson, Jorge Ferrer, William F. Mueller, Anke Busch, Klemens J. Hertel & Matthias Hebrok

Nature Cell Biology  16, 255–267 (2014) doi:10.1038/ncb2916
Received  16 October 2013 Accepted  10 January 2014 Published online  23 February 2014


Pancreatic ductal adenocarcinoma (PDA) develops through distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, genetic features resulting in IPMN-associated PDA (IPMN–PDA) versus PanIN-associated PDA (PanIN-PDA) are largely unknown. Here we find that loss of Brg1, a core subunit of SWI/SNF chromatin remodelling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA. Although Brg1-null IPMN–PDA develops rapidly, it possesses a distinct transcriptional profile compared with PanIN-PDA driven by mutant Kras and hemizygous p53 deletion. IPMN–PDA also is less lethal, mirroring prognostic trends in PDA patients. In addition, Brg1 deletion inhibits Kras-dependent PanIN development from adult acinar cells, but promotes Kras-driven preneoplastic transformation in adult duct cells. Therefore, this study implicates Brg1 as a determinant of context-dependent Kras-driven pancreatic tumorigenesis and suggests that chromatin remodelling may underlie the development of distinct PDA subsets.

Würde ich von Licht leben,
müßte ich grün sein.