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  • Articles: DFG German National Licenses  (2)
  • expression  (1)
  • immune memory  (1)
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  • Articles: DFG German National Licenses  (2)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 54 (1999), S. 135-146 
    ISSN: 1573-7217
    Keywords: stress ; protein ; expression ; human breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The stress‐inducible glucose regulated proteins (GRPs), a class of calcium‐binding molecular chaperones localized in the endoplasmic reticulum, have been implicated in the development of tumorigenicity, drug resistance, and cytotoxic immunology. This study investigates the expression pattern of GRP94 and GRP78 in a panel of breast carcinoma cell lines, as compared to two independently derived normal human breast epithelial cell lines. Here we report that a 3‐ to 5‐fold increase in the basal level of the GRP94 protein was observed in all five breast carcinoma cell lines examined. The increase was independent of either the p53 or estrogen receptor status of the breast carcinomas. In carcinoma cells deprived of glucose, mimicking the conditions in poorly vascularized solid tumors, up to 9‐fold induction of GRP94 was observed relative to the basal level expressed in a normal breast epithelial cell line. Interestingly, while the majority of the breast cancer cell lines can respond to tunicamycin‐ and thapsigargin‐induced stress by increasing the steady state levels of grp94 and grp78 transcripts, the induction at the GRP protein level is variable and does not always correspond with the transcript level. Further, we discovered that one of the human breast carcinoma cell lines, MCF‐7, has specifically lost its ability to respond to tunicamycin stress.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7217
    Keywords: breast cancer ; suicide gene therapy ; retroviral vector ; grp78 promoter ; immune memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gene therapy strategies employing the HSVtk/ganciclovir (GCV) suicide gene offer promising approaches towards the treatment of metastatic breast cancer. These include bystander effects on non-transduced tumor cells, lower systemic toxicity, and the possibility of inducing immunity against the tumor. Previously we have demonstrated the ability of the grp78 stress-inducible promoter to stimulate expression of reporter genes within the tumor microenvironment. However, experimental evidence demonstrating the ability of this promoter to activate therapeutic agents within the breast cancer environment causing tumor eradication is needed prior to clinical trials. In this report, we test the efficacy of the grp78 promoter in a retroviral system to drive the expression of the HSVtk suicide gene in a murine mammary adenocarcinoma cell line (TSA) in syngeneic, immune-competent hosts. Our results show that under glucose-starvation conditions in vitro, the expression of HSVtk and GCV induced cell death are enhanced in tumor cells in which the HSVtk gene is driven by the internal grp78 promoter compared to cells in which the Moloney murine leukemia virus LTR drives HSVtk. In in vivo studies, in tumors in which the HSVtk gene is driven by the grp78 promoter, GCV treatment causes complete tumor eradication, whereas tumors persist when the HSVtk gene is driven by the retroviral LTR. Our study suggests that the grp78 promoter may be useful to enhance the effectivity of therapeutic agents within a breast tumor. In addition, it is shown that immune memory is induced in syngeneic, immune-competent hosts. This new retroviral vector might therefore be useful for breast cancer gene therapy.
    Type of Medium: Electronic Resource
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