Galoforo S S, Berns C M, Erdos G, Corry P M, Lee Y J
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Mol Cell Biochem. 1996 Feb 23;155(2):163-71. doi: 10.1007/BF00229313.
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.
我们研究了降糖治疗对多药耐药人乳腺癌MCF-7/ADR细胞中AP-1转录因子激活及碱性成纤维细胞生长因子（bFGF）基因表达调控的影响。Northern印迹法和凝胶迁移率变动分析表明，降糖治疗可诱导c-jun和c-fos基因表达、AP-1结合活性以及bFGF基因表达。此外，与亲代细胞相比，表达高水平异常c-Jun蛋白的转染细胞中bFGF蛋白水平降低。一种有效的蛋白激酶C（PKC）抑制剂H-7（60微克/毫升）可抑制应激诱导的bFGF基因表达。我们的研究还表明，H-7不会促进bFGF mRNA的降解。因此，用H-7治疗对bFGF基因表达的抑制是由于该药物对bFGF mRNA合成的影响，而非bFGF mRNA的稳定性。我们的数据表明，低血糖诱导的bFGF基因表达是通过PKC和AP-1转录因子的激活介导的。
