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

• Published in: Molecular carcinogenesis Vol. 49; no. 6; pp. 592 - 602
• Main Authors: Przybyszewski, Joseph, Wang, Weiqun, Au, Angela, Perry, Courtney, Guetzko, Megan, Koehler, Ken, Birt, Diane F.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-06-2010
• Subjects: activator protein-1; Animals; Body Weight; Caloric Restriction; cancer prevention; Corticosterone - metabolism; DNA - metabolism; Epidermis - drug effects; Epidermis - pathology; Female; Glucocorticoids - metabolism; Mice; Mice, Inbred SENCAR; mouse epidermis; Protein Binding - drug effects; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - metabolism; Skin - drug effects; Skin - pathology; Skin Neoplasms - chemically induced; Skin Neoplasms - metabolism; Skin Neoplasms - prevention & control; Tetradecanoylphorbol Acetate; Transcription Factor AP-1 - metabolism; tumor promotion
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.20625

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. © 2010 Wiley‐Liss, Inc.