Inhibition of phorbol ester-induced AP-1-DNA binding, c-Jun protein and c-jun mRNA by dietary energy restriction is reversed by adrenalectomy in SENCAR mouse epidermis.
The aim of this study was to determine the effects of 40% dietary energy restriction (DER) relative to ad libitum feeding on AP-1-DNA binding and expression of c-Jun protein and c-jun mRNA in SENCAR mouse skin treated with acetone or 12-O-tetradecanoylphorbol 13-acetate (TPA). The role of the glucocorticoid hormone corticosterone (CCS) was investigated by adding CCS or vehicle control to the drinking water of adrenalectomized mice. AP-1-DNA binding, measured by electrophoretic mobility shift assay, showed that TPA treatment for 4 h increased AP-1-DNA binding by 2-fold over acetone controls (P < 0.05) and that DER reduced basal and TPA-induced AP-1-DNA binding in comparison with ad libitum fed groups in sham-operated mice (P < 0.05). TPA treatment increased c-Jun protein levels in control fed mice (4-fold) and in DER mice (2-fold) over basal levels 4 h post-treatment (P < 0.05). Analyzed over all groups, DER reduced c-Jun protein levels (P < 0.01) and this effect was reversed by adrenalectomy. TPA induction of c-jun mRNA was also reduced by DER compared with ad libitum fed mice (P < 0.05). Adrenalectomy and CCS supplementation demonstrated that the effects of DER on AP-1-DNA binding were mediated in part by CCS. Measurement of blood plasma CCS concentrations showed that: (i) DER increased CCS 5-fold over ad libitum fed mice in sham-operated animals (P < 0.05); (ii) adrenalectomy decreased CCS over sham-operated mice (P < 0.05); (iii) TPA treatment had no effect on CCS. Blood plasma IGF-I concentrations were unaffected by CCS modulation or TPA treatment but were decreased by DER compared with ad libitum fed mice (P < 0.05). Thus, dietary energy restriction may inhibit cancer mechanistically by reducing overall AP-1 transcription through a process that is mediated in part by glucocorticoid hormones.
Przybyszewski
J
J
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011-1061, USA.
Yaktine
A L
AL
Duysen
E
E
Blackwood
D
D
Wang
W
W
Au
A
A
Birt
D F
DF
D000315:Adrenalectomy; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004032:Diet; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D016758:Genes, jun / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D018632:Mice, Inbred SENCAR; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D007334:Insulin-Like Growth Factor I; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D003345:Corticosterone