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 fibrobl ast 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 gen e expression, AP-1 binding activity, as well as bFGF gene expression. Moreover, transfected cells expressing high levels of abnormal c-Jun p rotein exhibited a reduction in the bFGF protein levels compared to pa rental cells. A potent protein kinase C (PKC) inhibitor, H-7 (60 mu g/ 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 du e 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 th e AP-1 transcription factors.