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Updated: Oct 2, 2026
Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
JunB negatively regulates AP-1 activity and cell proliferation of malignant mouse keratinocytes
S Finch1, E Joseloff, T Bowden
1Department of Radiation Oncology, University of Arizona, Health Sciences Center, Rm. 4993, Arizona Cancer Center, 1515 N. Campbell, Tucson, AR 85724, USA.
Objective:
Previously we have shown that a malignant mouse keratinocyte cell line, 10Gy5, has elevated AP-1 transactivation and reduced JunB protein levels compared to its parental benign cell line, 308, and that the tumorigenicity in the 10Gy5 cells could be blocked by a dominant negative c-Jun mutant protein. We wished to determine whether the change in JunB protein levels could account for the elevated AP-1 activity and whether re-expression of JunB in malignant 10Gy5 cells altered their proliferative capacity.
Design:
In the current study, we reduced JunB expression in benign 308 cells with antisense oligonucleotides and increased JunB expression in malignant 10Gy5 cells by stable transfection of a JunB expression vector.
Results:
Increased AP-1 activity was detected after treatment of the benign 308 cell line with JunB antisense oligonucleotides that reduced JunB protein levels. Stably JunB-transfected clones of malignant 10Gy5 cells showed decreased AP-1 activity, slowed in vitro cell proliferation and reduced tumor growth when xenografted to athymic nude mice.
Conclusion:
These findings suggest that expression of JunB protein has a negative effect on malignant tumor cell proliferation in part through its ability to inhibit AP-1 transactivation.
Insights
JunB protein levels influence cancer cell activity. Lowering JunB increased AP-1 activity in benign cells, while restoring JunB in malignant cells reduced proliferation and tumor growth, suggesting JunB inhibits AP-1 transactivation.
Area of Science:
- Molecular biology
- Cancer research
- Cell biology
Background:
- Malignant keratinocyte cell lines exhibit elevated AP-1 transactivation and reduced JunB protein levels compared to benign counterparts.
- Tumorigenicity in malignant cells can be inhibited by dominant-negative c-Jun mutants.
Purpose of the Study:
- To investigate if JunB protein levels mediate elevated AP-1 activity.
- To determine if re-expressing JunB in malignant cells affects their proliferative capacity.
Main Methods:
- JunB expression was reduced in benign cells using antisense oligonucleotides.
- JunB expression was increased in malignant cells via stable transfection with a JunB expression vector.
Main Results:
- Reducing JunB in benign cells increased AP-1 activity.
- JunB re-expression in malignant cells decreased AP-1 activity, slowed proliferation, and reduced tumor growth in vivo.
Conclusions:
- JunB protein expression negatively impacts malignant tumor cell proliferation.
- JunB's inhibitory effect on AP-1 transactivation contributes to its anti-proliferative role.
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