JunB negatively regulates AP-1 activity and cell proliferation of malignant mouse keratinocytes.
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.


METHODS
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.


CONCLUSIONS
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.
Finch
S
S
Department of Radiation Oncology, University of Arizona, Health Sciences Center, Rm. 4993, Arizona Cancer Center, 1515 N. Campbell, Tucson, AR 85724, USA.
Joseloff
E
E
Bowden
T
T
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D018274:Electroporation; D005786:Gene Expression Regulation; D015603:Keratinocytes / Q000473:pathology*; D007700:Kinetics; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000235:genetics*; D015533:Transcriptional Activation; D014162:Transfection
D020319:Oligodeoxyribonucleotides, Antisense; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D015127:9,10-Dimethyl-1,2-benzanthracene