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Intestinal tumor progression is associated with altered function of KLF5
Nicholas W Bateman1, Dongfeng Tan, Richard G Pestell
1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA.
The Journal of Biological Chemistry
|January 17, 2004
Summary
Krüppel-like factor 5 (KLF5) promotes growth in normal intestinal cells but inhibits it in colon cancer cells. Intestinal tumors down-regulate KLF5 expression, suggesting a role in tumorigenesis.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Krüppel-like transcription factors (KLFs) are implicated in cell growth and cancer.
- KLF5 is expressed in proliferating intestinal crypt cells, suggesting a growth-promoting role.
Purpose of the Study:
- To investigate the role of KLF5 in intestinal epithelial cells and colon cancer.
- To determine how KLF5 function and expression change during intestinal tumor progression.
Main Methods:
- Studied KLF5 effects on colony formation, cyclin D1 transcription, and cell growth in normal and cancer intestinal cell lines.
- Utilized Ras-mediated transformation to model intestinal tumor progression.
- Analyzed KLF5 mRNA and protein levels in tumors from mouse models and human adenomas.
Main Results:
- KLF5 enhanced growth and cyclin D1 transcription in normal cells but inhibited them in colon cancer cells.
- Ras-transformation altered KLF5 function and led to its down-regulation.
- KLF5 expression was reduced in intestinal tumors, including APC(min) mice and human adenomas.
Conclusions:
- Intestinal tumor progression is associated with altered KLF5 function.
- KLF5 expression is down-regulated in intestinal tumors through multiple mechanisms.
- KLF5 plays a complex role in intestinal tumorigenesis, with its function shifting from growth promotion to inhibition.