Related Experiment Video

Updated: Sep 30, 2026

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
05:21

Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy

Published on: October 6, 2014

Carcinogen-induced pancreatic lesions in the mouse: effect of Smad4 and Apc genotypes

Jan Cullingworth1, Martin L Hooper, David J Harrison

  • 1Sir Alastair Currie Cancer Research UK Laboratories, Molecular Medicine Centre, Western General Hospital, Edinburgh EH4 2XU, UK.

Oncogene
|July 4, 2002
PubMed

Insights

Mutations in SMAD4 and APC genes are linked to pancreatic cancer. Co-inhibiting these genes in mice increases abnormal pancreatic foci, suggesting a link between TGF-beta and Wnt pathways in tumor suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Mutations in tumor suppressor genes SMAD4 and APC are implicated in human pancreatic cancer.
  • Abnormal foci in pancreatic acinar cells, characterized by increased beta-catenin, are precursors to pancreatic neoplasia.

Purpose of the Study:

  • To investigate the functional cooperation between TGF-beta and Wnt signaling pathways in pancreatic tumorigenesis.
  • To determine the role of SMAD4 and APC gene mutations in the development of pancreatic abnormalities.

Main Methods:

  • Treatment of wild-type, Smad4(+/-), Apc(Min/+), and Apc(Min/+)Smad4(+/-) mice with N-Nitroso-N-Methyl Urea (NMU).
  • Analysis of abnormal pancreatic foci, including size, number, and morphological nuclear atypia.
  • Assessment of beta-catenin levels in pancreatic acinar cells.

Main Results:

  • NMU treatment induced abnormal foci in all mouse groups.
  • Only NMU-treated Apc(Min/+)Smad4(+/-) mice showed a significant increase in abnormal pancreas.
  • The increase in abnormal pancreas was attributed to a higher number of abnormal foci, not increased focus size.
  • Smaller abnormal foci exhibited morphological nuclear atypia.

Conclusions:

  • Functional cooperation between TGF-beta and Wnt signaling pathways suppresses pancreatic tumorigenesis in mice.
  • The combined loss of SMAD4 and APC function promotes pancreatic neoplasia through an increased number of precursor lesions.

More Related Videos

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer06:01

A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer

Published on: July 6, 2017

Cell Population Analyses During Skin Carcinogenesis06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

Related Concept Videos

Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...