Journal of Biological Chemistry
Volume 270, Issue 48, 1 December 1995, Pages 28790-28796
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Cell Biology and Metabolism
Effect of Ionizing Radiation on AP-1 Binding Activity and Basic Fibroblast Growth Factor Gene Expression in Drug-sensitive Human Breast Carcinoma MCF-7 and Multidrug-resistant MCF-7/ADR Cells *1

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We studied the effect of ionizing radiation on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in drug-sensitive human breast carcinoma (MCF-7) cells and its drug-resistant variant (MCF-7/ADR) cells. Northern blot and gel mobility shift assays showed that 135 cGy of ionizing radiation induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression in MCF-7/ADR cells. In MCF-7 cells, however, we observed little/no induction of bFGF gene expression and AP-1 binding activity after the stress. Nevertheless, MCF-7 cells transfected with plasmids containing c-jun gene contain high levels of bFGF protein. H-7 (60 μg/ml), a potent protein kinase C (PKC) inhibitor, inhibited the stress-induced AP-1 binding activity and bFGF gene expression in MCF-7/ADR cells. Corroborating this observation, overexpression of PKCα induced bFGF gene expression in MCF-7 cells. Taken together, these results suggest that stress-induced bFGF gene expression is mediated through the activation of PKC and AP-1 transcription factors. Differences in the levels of PKC activity and AP-1 binding factors may be responsible for differential expression of bFGF among breast cancer cell lines. Although there are large differences in response to ionizing radiation between MCF-7 and MCF-7/ADR cell lines, we observed no significant differences in radiocytotoxicity between them.

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1

The abbreviations and trivial names used are:

    bFGF

    basic fibroblast growth factor

    TPA

    12-O-tetradecanoylphorbol-13-acetate

    TRE

    TPA response element

    Gy

    gray

    PBS

    phosphate-buffered saline

    PAGE

    polyacrylamide gel electrophoresis

    PKC

    protein kinase C

    GAPDH

    glyceraldehyde-3-phosphate dehydrogenase

    kb

    kilobase(s)

    SRE

    serum response element

    TCF

    ternary complex factor

    H-7

    1-(5-isoquinolinesulfonyl)-2-methylpiperazine

    HA1004

    N-(2-guanidinoethyl)-5-isoquinolinesulfonamide.

*

This research was supported by National Cancer Institute Grants CA48000 and CA44550, William Beaumont Hospital Research Institute Grants 94-15 and 95-07, and the Elsa U. Pardee Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.