Journal Article

Inhibition of phorbol ester-induced AP-1–DNA binding, c-Jun protein and c-<i>jun</i> mRNA by dietary energy restriction is reversed by adrenalectomy in SENCAR mouse epidermis

Joseph Przybyszewski, Ann L. Yaktine, Ellen Duysen, Darcy Blackwood, Weiqun Wang, Angela Au and Diane F. Birt

in Carcinogenesis

Volume 22, issue 9, pages 1421-1427
Published in print September 2001 | ISSN: 0143-3334
Published online September 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.9.1421
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

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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.

Keywords: ANOVA, analysis of variance; CCS, corticosterone; DER, dietary energy restriction; DTT, dithiothreitol; EMSA, electrophoretic mobility shift assay; GR, glucocorticoid receptor; HBSSE, Hank's balanced salt solution containing 0.08% EDTA; IGF-I, insulin-like growth factor I; PKC, protein kinase C; PMSF, phenylmethylsulfonyl fluoride; TPA, 12-O-tetradecanoylphorbol 13-acetate; TRE, TPA response elements.

Journal Article.  5971 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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