Hypoglycemia-induced AP-1 transcription factor and basic fibroblast growth factor gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells.
We investigated the effect of hypoglycemic treatment on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. Northern blot and gel mobility shift assays showed that hypoglycemic treatment induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression. Moreover, transfected cells expressing high levels of abnormal c-Jun protein exhibited a reduction in the bFGF protein levels compared to parental cells. A potent protein kinase C (PKC) inhibitor, H-7 (60 micrograms/ml) suppressed the stress-induced bFGF gene expression. Our study also demonstrated that H-7 did not facilitate the decay of bFGF mRNA. Thus, the suppression of bFGF gene expression by treatment with H-7 was due to the effect of the drug on the synthesis of bFGF mRNA rather than the stability of bFGF mRNA. Our data suggest that hypoglycemia-induced bFGF gene expression is mediated through the activation of PKC and the AP-1 transcription factors.
Galoforo
S S
SS
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Berns
C M
CM
Erdos
G
G
Corry
P M
PM
Lee
Y J
YJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001483:Base Sequence; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008969:Molecular Sequence Data; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018808:Transcription Factor AP-1 / Q000235:genetics*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010879:Piperazines; D018808:Transcription Factor AP-1; D016222:Fibroblast Growth Factor 2; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C