Related Experiment Video
Updated: Jun 16, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
SGK1-dependent intestinal tumor growth in APC-deficient mice
Kan Wang1, Shuchen Gu, Omaima Nasir
1Department of Physiology, University of Tuebingen, 72076 Tuebingen, Germany.
Abstract:
Adenomatous polyposis coli (APC) is inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying defective APC (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC binds GSK3beta, which phosphorylates beta-catenin thus fostering its degradation. beta-catenin upregulates the serum- and glucocorticoid-inducible kinase Sgk1, which inhibits GSK3beta. The present study explored the role of SGK1 in tumor growth of apc(Min/+)mice. apc(Min/+)mice were crossed with SGK1-knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) generating apc(Min/+)/sgk1(-/-)mice and apc(Min/+)/sgk1(+/+)mice. beta-catenin abundance was determined by Western blotting and confocal microscopy. As a result apc(Min/+)/sgk1(+/+)mice developed significantly more intestinal tumors than apc(Min/+)/sgk1(-/-)mice. Following chemical cancerogenesis, colonic beta-catenin protein abundance was significantly higher in sgk1(+/+)mice than in sgk1(-/-)mice. beta-catenin expression was significantly increased in HEK293 cells treated with dexamethasone for upregulation of Sgk1. In conclusion, SGK1 expression favors the development of intestinal tumors in APC-deficient mice, an effect at least partially due to enhanced beta-catenin protein abundance.
Insights
Serum- and glucocorticoid-inducible kinase 1 (SGK1) promotes intestinal tumor growth in mice with defective Adenomatous polyposis coli (APC). SGK1 increases beta-catenin levels, contributing to tumor development in APC-deficient models.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Adenomatous polyposis coli (APC) gene inactivation is critical in colorectal cancer development.
- APC deficiency leads to beta-catenin accumulation and promotes tumor formation.
- Serum- and glucocorticoid-inducible kinase 1 (SGK1) is regulated by beta-catenin and influences cell signaling pathways.
Purpose of the Study:
- To investigate the role of SGK1 in tumor development in a mouse model of APC deficiency.
- To determine the impact of SGK1 on beta-catenin protein levels in the context of APC mutations.
Main Methods:
- Generation of apc(Min/+) mice crossed with SGK1-knockout (sgk1(-/-)) and wild-type (sgk1(+/+)) littermates.
- Quantification of beta-catenin abundance using Western blotting and confocal microscopy.
- Assessment of tumor development and beta-catenin levels following chemical carcinogenesis.
Main Results:
- Mice with functional SGK1 (apc(Min/+)/sgk1(+/+)) developed significantly more intestinal tumors than SGK1-deficient mice (apc(Min/+)/sgk1(-/-)).
- Beta-catenin protein levels were significantly higher in SGK1-expressing mice compared to SGK1-knockout mice.
- SGK1 upregulation in HEK293 cells led to increased beta-catenin expression.
Conclusions:
- SGK1 expression promotes intestinal tumor development in APC-deficient mice.
- This pro-tumorigenic effect of SGK1 is, at least partially, mediated by increased beta-catenin protein abundance.
