Dietary energy restriction, in part through glucocorticoid hormones, mediates the impact of 12-O-tetradecanoylphorbol-13-acetate on jun D and fra-1 in Sencar mouse epidermis.
Dietary energy restriction (DER, 40% calorie reduction from fat and carbohydrate) inhibited mouse skin carcinogenesis and decreased 12-O-tetradecanoyl-13-phorbol acetate (TPA)-induced activator protein-1 (AP-1):DNA binding previously. This study measured protein levels of c-jun, jun B, jun D, c-fos, fra-1, and fra-2 and examined their contribution to AP-1:DNA binding by electrophoretic mobility shift assay (EMSA) with supershift analysis in the epidermis of control and DER Sencar mice exposed to TPA. TPA significantly increased c-jun, jun B, c-fos, fra-1, and fra-2 and decreased jun D within 3-6 h after treatment. AP-1:DNA binding reached a maximum 2.5-fold induction over controls 4 h after TPA treatment and antibodies to jun B, jun D, and fra-2 in the EMSA binding reaction resulted in supershifts in both acetone- and TPA-treated mice 1-6 h after treatment. The effect of corticosterone (CCS) and DER on the AP-1 proteins and on the composition of the AP-1:DNA complex was measured in adrenalectomized (adx) mice. DER reduced the TPA impact on jun D and enhanced the induction of fra-1. In addition, CCS-supplemented groups had significantly lower jun D and higher fra-2 than adx groups and sham groups. While sham animals treated with either acetone or TPA contained jun B, jun D, and fra-2 proteins in the AP-1:DNA complex by supershift analysis, fra-2 was no longer seen in adx DER animals. In summary, our study supports potential roles for jun D, jun B, and fra-1 in the DER regulation of AP-1 function in the Sencar mouse skin carcinogenesis model.
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA.
Joseph
J
Przybyszewski
Weiqun
W
Wang
Angela
A
Au
Courtney
C
Perry
Megan
M
Guetzko
Ken
K
Koehler
Diane F
DF
Birt
D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D003345:Corticosterone / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D051379:Mice; D018632:Mice, Inbred SENCAR; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000378:metabolism; D000099169:Fos-Related Antigen 1
D003345:Corticosterone; D004247:DNA; D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1