Kras Upregulates Notch Signaling to Induce Gallbladder Tumorigenesis in Mice

Overview

Journal Oncoscience

Specialty Oncology

Date 2017 Nov 17

PMID 29142904

Citations 8

Authors

Wen-Cheng Chung

Junqing Wang

Yunyun Zhou

Keli Xu

Affiliations

Soon will be listed here.

Abstract

Background: Kras mutations and increased Notch activation occur frequently in gallbladder cancer. However, their roles in gallbladder carcinogenesis have not been defined. This study was aimed at determining whether expression of mutant Kras was sufficient to induce gallbladder carcinoma and whether Notch deregulation played a role in this context.

Methods: We determined Cre recombination activity of in the gallbladder using a reporter strain and examined gallbladder tumor development in the mice. We analyzed expression of Notch pathway genes in the mouse gallbladder by immunohistochemistry, quantitative RT-PCR, and Western blot analysis. We also determined the effect of deletion on Kras-induced gallbladder tumor development.

Results: exhibits robust recombination activity in the gallbladder epithelium. mice form early onset adenoma in the gallbladder and adjacent biliary tract with complete penetrance, albeit short of invasive adenocarcinoma. Kras upregulates expressions of , and downstream target genes , and , and deletion of partially suppresses Kras-induced adenoma development.

Conclusions: Kras induces gallbladder adenoma and Notch plays a key role in Kras-initiated gallbladder tumorigenesis.

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