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

Yj, Lee; Ss, Galoforo; Cm, Berns; Erdö́s, G.; Ak, Gupta; Ways, D. Kirk; Pm, Corry

doi:10.1074/jbc.270.48.28790

Cited by 57 publications

(23 citation statements)

References 52 publications

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“…Ionizing radiation induce various growth factors and cytokines, including TNF-a, IL-1, FGF, and PDGFa. A relation between the basic ®broblast growth factor and AP-1 transcription factor has been reported (Lee et al, 1995). In fact, ionizing radiation induced bFGF expression in human breast carcinoma cells that was mediated through the activation of AP-1.…”

Section: Radiation-induced Tgf-b1 Gene Expressionmentioning

confidence: 98%

Coactivation of AP-1 activity and TGF-β1 gene expression in the stress response of normal skin cells to ionizing radiation

et al. 1997

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Activation of the AP-1 transcription factor and TGF-b1 growth factor by ionizing radiation was studied both in vivo in pig skin, and in vitro in human ®broblasts and keratinocytes. Three and 6 h after irradiation, the Fos and Jun proteins and their binding activity to an AP-1 consensus sequence were strongly induced by high doses of g-rays. c-Fos, c-Jun and JunB proteins were found to be present in gel-shift complexes by probing with speci®c antibodies. Both keratinocytes and ®broblasts exhibited heightened AP-1 activity following irradiation. As we previously found that TGF-b1 is involved in the development of skin lesions induced by radiation, TGFb1 gene expression was also examined. Two and 6 h after irradiation, the levels of TGF-b1 transcripts were increased in skin. By immunostaining, TGF-b1 protein levels were found to be increased in ®broblasts, keratinocytes and endothelial cells. As the TGF-b1 promoter contains AP-1 binding sites, the relation between AP-1 activity and TGF-b1 induction was addressed. The 7365 TGF-b1 promoter fragment, which contains a high anity AP-1 site, exhibited increased binding to Jun and Fos proteins following irradiation. These results suggest that stress-inducible TGF-b1 expression is mediated by the activation of AP-1 transcription factor.

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Section: Radiation-induced Tgf-b1 Gene Expressionmentioning

confidence: 98%

Coactivation of AP-1 activity and TGF-β1 gene expression in the stress response of normal skin cells to ionizing radiation

et al. 1997

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“…Quantitation of HSF-HSE Binding Activity-Conditions for the gel mobility shift assay, a description of the 32 P-labeled HSE oligonucleotide, and preparation of whole cell extracts were as published previously (31)(32)(33). A double-stranded HSE (upper strand 5Ј-CTTAAC-GAGAGAAGGTTCCAGATGAGGGCTGAA-3Ј, Ref.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Oxidative Stress-induced HSP70 Gene Expression Is Mediated through SAPK Pathway

Lee¹,

Corry²

1998

Journal of Biological Chemistry

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In previous reports we demonstrated that glucose deprivation induces metabolic oxidative stress in drugresistant human breast carcinoma MCF-7/ADR cells (Lee, Y. J., Galoforo, S. S., Berns, c. M., Chen, J. C., Davis, B. H., Swim, J. E., Corry, P. M., and Spitz, D. R. (1998) J. Biol. Chem. 273, 5294 -5299). In the study described here, we investigated intracellular responses to metabolic oxidative stress. Northern blots show an increase in the level of HSP70 and HSP28 mRNA in cells exposed to glucose-free medium for 1 h. One-and two-dimensional polyacrylamide gel analyses confirmed that glucose deprivation induced a family of HSPs, particularly an inducible HSP70. Overexpression of bcl-2 suppressed glucose deprivation-induced HSP70 gene expression, heat shock transcription factor-heat shock element binding activity, as well as c-Jun NH 2 -terminal kinase (JNK1) activation. Expression of a dominant-negative mutant of JNK1 also suppressed glucose deprivationinduced JNK1 activation as well as HSP70 gene expression. Taken together, the stress-activated protein kinase signal transduction pathway is involved in glucose deprivation-induced heat shock gene expression.It is well established that the transcriptional induction of heat shock genes in eukaryotes is mediated by the heat shock transcription factor (HSF) 1 (1-8). This protein can be activated by a variety of stresses such as heat shock, heavy metals, or arsenite (4, 9 -11). The activated HSF binds to the promoters which contain the heat shock element (HSE) and then stimulates transcription (1,5,12). A fundamental question which remains unanswered is how these stresses activate HSF. HSF is phosphorylated under normal growth conditions and is hyperphosphorylated subsequent to stress. It has been proposed that such phosphorylation may be mediated through the MAP kinase family such as c-Jun NH 2 -terminal kinase (JNK) (13).Several reports have demonstrated that the JNK, also referred to as stress-activated protein kinase (SAPK), signal transduction pathway can be activated by oxidative stress (14 -16). Following activation, JNK phosphorylates several transcription factors including activating transcription factor-2 (17), Elk-1 (18), , and c-Jun (20) which are involved in regulating numerous genes implicated in cell proliferation, transformation, differentiation, and DNA repair (21-24). Recent studies also show that oxidative stress can activate HSF and increase HSP70 gene expression (25). These observations suggest a possibility that oxidative stress-induced activation of HSF is mediated through the SAPK pathway.We have previously observed that glucose deprivation increases intracellular hydroperoxide production and oxidized glutathione in drug-resistant human breast carcinoma MCF-7/ ADR cells (26). These results led us to investigate the possibility that glucose deprivation-induced metabolic oxidative stress may activate HSF through the SAPK pathway and result in hsp gene expression. In this study, we demonstrate that glucose deprivation induces HSP genes, in partic...

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“…It seems that this level of P-gp expression in MCF-7 cannot be ignored, even though this cell line is reported to be sensitive to chemotherapy. 26 effect of csa on cell uptake of free DOX and liposomal DOX First, we studied the effect of free CsA on the internalization of free DOX in MCF-7 and MCF-7/ADR cells by flow cytometry. As seen in Figure 3, the DOX level in the MCF-7/ ADR cell line was lower than that in MCF-7, due to the different levels of P-gp expression.…”

Section: P-gp Expression In Mcf-7 Cell Linementioning

confidence: 99%

The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression

Gao¹,

Lin²,

Chen³

et al. 2014

IJN

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Introduction P-glycoprotein (P-gp) inhibitors are usually used to treat tumors that overexpress P-gps. However, most common types of breast cancers, such as Luminal A, are low-P-gp expressing, at least during the initial phases of treatment. Therefore, it would be interesting to know if P-gp inhibitors are still useful in treating low-P-gp-expressing tumors. Methods In the study reported here, the human breast-cancer cell line MCF-7, chosen as a model of Luminal A, was found to be low-P-gp expressing. We designed a novel doxorubicin (DOX) sterically stabilized liposome system co-loaded with the low-dose P-gp inhibitor cyclosporine A (CsA) (DOX/CsA/SSL). Results The co-delivery system showed good size uniformity, high encapsulation efficiency, and a desirable release profile. The cell-uptake and cytotoxicity studies demonstrated that CsA could significantly enhance the intracellular accumulation and toxicity of free DOX and the liposomal DOX in MCF-7 cells. The confocal microscopy and in vivo imaging study confirmed the intracellular and in vivo targeting effect of DOX/CsA/SSL, respectively. Finally, the in vivo study proved that DOX/CsA/SSL could achieve significantly better antitumor effect against MCF-7 tumor than controls, without inducing obvious systemic toxicity. Conclusion This study demonstrated that the co-delivery of a low-dose P-gp inhibitor and liposomal DOX could improve the therapy of low-P-gp-expressing cancer, which is of significance in clinical tumor therapy.

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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

Cited by 57 publications

References 52 publications

Coactivation of AP-1 activity and TGF-β1 gene expression in the stress response of normal skin cells to ionizing radiation

Coactivation of AP-1 activity and TGF-β1 gene expression in the stress response of normal skin cells to ionizing radiation

Metabolic Oxidative Stress-induced HSP70 Gene Expression Is Mediated through SAPK Pathway

The co-delivery of a low-dose P-glycoprotein inhibitor with doxorubicin sterically stabilized liposomes against breast cancer with low P-glycoprotein expression

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