English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Pancreatic ductal adenocarcinoma (PDAC) is an almost uniformly lethal disease in humans. Transforming growth factor-β (TGF-β) signaling plays an important role in PDAC progression, as indicated by the fact that  Smad4 , which encodes a central signal mediator downstream from TGF-β, is deleted or mutated in 55% and the  type II TGF-β receptor  ( Tgfbr2 ) gene is altered in a smaller subset of human PDAC. Pancreas-specific  Tgfbr2  knockout mice have been generated, alone or in the context of active  Kras  ( Kras G12D  ) expression, using the Cre-loxP system driven by the endogenous  Ptf1a  ( pancreatic transcription factor-1a ) locus. Pancreas-selective  Tgfbr2  knockout alone gave no discernable phenotype in 1.5 yr. Pancreas-specific  Kras G12D   activation alone essentially generated only intraepithelial neoplasia within 1 yr. In contrast, the  Tgfbr2  knockout combined with  Kras G12D   expression developed well-differentiated PDAC with 100% penetrance and a median survival of 59 d. Heterozygous deletion of  Tgfbr2  with  Kras G12D   expression also developed PDAC, which indicated a haploinsufficiency of TGF-β signaling in this genetic context. The clinical and histopathological manifestations of the combined  Kras G12D   expression and  Tgfbr2  knockout mice recapitulated human PDAC. The data show that blockade of TGF-β signaling and activated Ras signaling cooperate to promote PDAC progression.

genes and development

Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression